Clin Auton Res (2003) 13 : 54–74 © Steinkopff Verlag 2003

ABSTRACTS

Third International Workshop on: THE HUMAN CIRCULATION: Noninvasive Haemodynamic, Autonomic and Vascular Monitoring 9th to the 11th of May, 2003 Minorites Monastery, “Minoritenkloster” Mariahilfer Platz 3, 8020 Graz, Austria Graz: Cultural Capital of Europe 2003 Organized by: Department of Internal Medicine, Hospital Barmherzige Brüder, Teaching Hospital of the Karl Franzens University, Institute of Biochemistry, Karl-Franzens University Graz on behalf of the Austrian Society of Hypertension and on behalf of the Working Group for Endothelial Function and Atherosclerosis of the Austrian Society of Cardiology. Local Organization: Univ. Prof. Dr. Falko Skrabal Secretarial Office: Dr. Harald Mayer, Dr. Richard Rudnicki, Dr. Wolfgang Urban Department of Internal Medicine Krankenhaus der Barmherzigen Brüder Teaching Hospital of the Karl Franzens University Marschallgasse 12, A-8020 Graz E-Mail: [email protected] Web: www.noninvasive-monitoring.at Fax: +43-3 16/7 06 75 98 Tel.: +43-6 99/12 82 87 61 Faculty: Prof. J. Cockcroft (Cardiff, UK) Prof. W. Graier (Graz, Austria) Prof. Th. Kenner (Graz, Austria) Prof. G. Kostner (Graz, Austria) Prof. C. J. Mathias (London, UK) Prof. G. Parati (Milano, Italy) Prof. F. Skrabal (Graz, Austria) Prof. I. Wilkinson (Cambridge, UK)

Topics:  Noninvasive Assessment of Cardiac Output and Beat to Beat Blood Pressure  Autonomic Assessment (Heart Rate Variability, Blood Pressure Variability, Sympathico-Vagal Balance, Baroreceptor Reflex Sensitivity)  Pulse Wave Analysis and Assessment of Endothelial Function  Early Detection of Atherosclerosis  Assessment of Cardiovascular Risk  Physiological, Pathophysiological, Clinical and Pharmacological Aspects State of the Art Lectures:  The autonomic nervous system and cardiovascular disturbances; differential therapeutic implications (C. J. Mathias)  Evaluating ANS function: a research tool only or a clinically useful procedure? (G. Parati)  Evaluation of the Barorecptor Reflex (G. Parati)  Advantages of Complete Haemodynamic Monitoring (F. Skrabal)  Pulse Wave Analysis and it’s clinical Significance (J. Cockcroft)  Controversies in Pulse Wave Analysis (I. Wilkinson)  Update on Flow Mediated Vasodilation (Th. C. Wascher)  Signal transduction in the endothelium (W. F. Graier)

3rd Int. Workshop on Noninvasive Monitoring

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The Autonomic Nervous System

Ageing attenuates the cardiac but not the vascular limb of the arterial baroreflex

Evaluation of baroreflex sensitivity should be corrected for HR

Brown CM, Sanya EO, Weih A, Neundörfer B, Hilz MJ Dept of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany

Christina Abrahamsson*, Lars Lind**, Catherine Åhlund**, Margareta Nordlander* * Integrative Pharmacology, **Experimental Medicine AstraZeneca R & D Mölndal Purpose of the Study: To study baroreflex sensitivity (BRS) in healthy volunteers during stress and physical activity. Methods: BRS was measured with the sequence method in ten healthy subjects during rest, breathing at 0.1 Hz, mental stress, cold stress, standing and bicycle exercise. Results: BRS decreased during interventions which increased heart rate (HR).When BRS was plotted against HR, BRS decreased exponentially as HR increased. The relationship between the two variables appeared linear when a logarithmic scale was used for BRS. The exponential relationship between BRS and HR was highly significant for each individual subject in the study and was linear when the natural logarithm of BRS (lnBRS) was used.Accordingly, the relationship between lnBRS and HR for each individual could be described by a straight line fitted to the data by using linear regression. The slopes of the lnBRS-HR relationships were similar, but the intercepts varied between the subjects. The linear equation for the lnBRS-HR relationship was used to standardize BRS at a HR commonly found at rest, 60 bpm (BRS[60]), ranging from 7 to 27 ms/mmHg for the subjects in the study. Conclusion: The present study emphasizes the importance of measurements of BRS at different HRs in each individual in order to determine the individual lnBRS-HR relationship, which subsequently can be used to calculate BRS at a certain HR. Thereby, by standardizing BRS for HR, the dramatic impact of a small change in HR on the BRS which occurs at lower HRs, can be avoided. This is of particular importance when comparing groups of patients regarding BRS or when examining the effect of drugs or other interventions on BRS during which the HR change.

Two different adaptations to active orthostasis in essential hypertension Bettencourt MJ, Gomes-Pinto B, Oliveira EI, Silva-Carvalho L Laboratório Moniz de Bettencourt, Instituto de Fisiologia, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, 1649–028 Lisbon, Portugal Purpose of the Study: It was our intention to study the adaptations to active orthostasis in hypertensive patients and to search for patterns that might reveal the underlying dysfunction. Methods: Using the electrical Bioimpedance-Bomed NCCOM3assembly,we measured cardiac output,stroke volume, heart rate (HR), inotropic index (INOI), total vascular resistance, cardiac work and aortic compliance in sixty patients with essential hypertension in the supine position (su) and in the active standing position (as). Results: For each cardiovascular variable, we found a linear correlation of the values for as vs. su in two different fashions: one correlation corresponded to the younger patients, the other to the elderly ones. Except for HR, both sets of values differed from the ones of healthy subjects. Conclusion: These results suggest, that in younger patients there is a decrease of the influence of cardiopulmonary reflexes for the maintenance of autonomic balance,while in elderly patients there seems to be an impairment of the carotid baroreflex. They also show, that, as far as the control by the autonomic nervous system is concerned, one circulatory status is favoured over the other.

Purpose of the Study: Several studies have shown that baroreflexmediated vagal control of the heart deteriorates with age but there is little information about the effect of ageing on sympatheticallymediated baroreflex control of the blood vessels. The aim of this study was to assess the effects of ageing on baroreflex control of the heart rate and blood vessels. Methods: In 40 healthy volunteers, age 20–87 yrs, we applied oscillatory neck suction (0 to –30 mmHg) at 0.1 Hz to assess the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was maintained at 0.25 Hz. Blood pressure, RR-intervals and respiration were recorded continuously. Spectral analysis was used to evaluate the magnitude of the low frequency (0.03–0.14 Hz) and high frequency (0.15–0.50 Hz) oscillations in RR-interval and blood pressure.Responses to neck suction were assessed as the change in the power of the RR-interval and blood pressure fluctuations at the stimulation frequency from baseline values. Results: Resting low and high frequency powers of RR-interval decreased significantly with age (P < 0.01). However, the low frequency power of blood pressure did not correlate with age. Spontaneous baroreflex sensitivity showed a significant inverse correlation with age (r = –0.46, P < 0.05). Responses of RR-interval and systolic blood pressure to 0.1 Hz neck suction stimulation were not related to age but the RR-interval response to 0.2 Hz neck suction declined significantly with age (r = –0.61, P < 0.01). Conclusion: These results confirm an age-related decrease in cardiovagal baroreflex responses. However, sympathetically-mediated baroreflex control of the blood vessels is preserved with age.

Automatic measurement of spontaneous baroreflex sensitivity with the Task Force Monitor® for detection of autonomic dysfunction in diabetes mellitus S. Eckert, N. Lotz, Ch. Bergemann, B. Kemper, R. Petzoldt, D. Horstkotte Heart and Diabetes Center North Rhine-Westphalia, Ruhr University of Bochum, Bad Oeynhausen, Germany Purpose of the Study: Diabetic autonomic dysfunction is associated with a high risk of mortality. Several clinical trials have shown that reduced baroreflex sensitivity (BRS) is an independent risk factor affecting outcome after acute cardiovascular events. Identification of autonomic abnormalities in patients with diabetes with a battery of standardized tests is time consuming. Therefore, a single test would be advantageous. The aim of our study was to compare the detection of autonomic dysfunction by classical laboratory autonomic dysfunction tests (PROSCICARD) with spontaneous BRS measured automatically with the new Task Force Monitor® in diabetic patients. The estimates can be obtained by short non-invasive recordings of blood pressure (BP) and heart rate (duration 10 minutes) in the supine patient under conditions suitable for routine outpatient evaluation. Methods: We compared the results of 5 age-matched diabetic patients with abnormal autonomic function tests (D) and with those of 10 healthy age-matched control subjects (C). Results: A good correlation was found in C compared to TANK (AJH 200): 16 ± 10 ms/mmHg (males, aged 30–39 ys.). Compared to C, BRS values for increasing systolic BP in supine position was markedly less in D (16 ms/mmHg vs. 5 ms/mmHg).

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Age (years) Body mass index (kg/qm) BRS (ms/mmHg)

C

D

p-value

34±3 26±2 16±3

35±2 24±1 5±1

0.53 0.5 0.01

Conclusion: BRS can be easily and non-invasively measured with the Task Force Monitor&Pfeil;. Reduced BRS values indicate autonomic dysfunction in diabetes mellitus.

Reproducibility of temporal QT variability

Group A consisted of 410 men, age 43.1±16.5 yrs and 590 women, 40.5±17.1 yrs; 584 were HUT positive. Group B consisted of 423 men, age 40.4±17.7 yrs and 577 women age 37.0±18.2 yrs;191 were HUT positive. Results: Arrhythmias occurred in 340 patients (n = 2000); (186 patients with positive HUT and 154 patients with negative HUT). In 62 patients (n = 186) arrhythmias were present independetly of the syncope (56 having premature beats). In 124 patients (n = 186) arrhythmias occurred just before or immediately after syncope: premature beats in 78 patients, asystolic pause > 5 seconds in 22 patients, asystolic pause < 5 seconds in 12 patients; one patient with nodal rhythm and one patient with atrial fibrillation. Conclusion: Arrhythmias may be provoked by positive HUT (arrhythmias were recorded in 17 % of our 2000 patients), that are mostly benign, predominantly premature beats.Asystolic pauses are to be expected and may be very long; therefore, careful monitoring is mandatory.

S. Gao, M. Johansson, A. Hammarén, M. Nordberg, P. Friberg Cardiovascular Institute, Clinical Physiology, Sahlgrenska University Hospital, Göteborg, Sweden Purpose of the Study: Temporal QT variability index (QTVI) is a predictor of ventricular arrhythmia and sudden cardiac death in congestive heart failure patients. Little is known about the reproducibility of the temporal QTVI measurements. In the present study we investigated the intra-, inter-observer and within-subject (between recordings on two different days) variability of the QTVI measurement in 27 healthy subjects. Methods: ECG was recorded on two occasions with a mean interinvestigation interval of 8 ± 7 days. An operator-defined QT interval template for one beat was set and the mean QT interval was determined using a computer-derived algorithm. QT variance, RR interval and RR variance were measured. QTVI was calculated as the log ratio between normalized QT- and RR interval variability. Two independent observers assessed temporal QTVI in the same 5-minute epoch in both recordings. Results: The intra-, inter-observer and within-subject variability of QTVI, calculated as the coefficient of variation, was 6.7, 4.5 and 18.3 %, respectively. The intra-, inter-observer and within-subject Lin’s concordance correlation coefficient was 0.91, 0.98 and 0.56, respectively. The within-subject variability of RR variance was 49.4 %. Conclusion: The intra- and inter-observer variabilty of temporal QTVI was low, indicating a good reproducibility of the temporal QTVI measurement. The within-subject variability between two days was somewhat higher, partly due to differences in the heart rate variability. This within-subject variability should be taken into consideration when longitudinal assessment of QTVI is studied.

How dangerous is the head-up tilt-table test? Grad A, Kermavnar MT, Meglicˇ B, Benko F, Sˇvigelj V. Medical Center Ljubljana, Dept. of Neurology, Ljubljana, Slovenia Purpose of the Study: Head-up tilt-table test (HUT) is the gold standard of diagnosis in patient with syncope of unknow origin. The test is positive if a patient experienced the same symptoms as spontaneously during the hemodynamic changes provoked by tilting. To increase the sensitivity of the test, the administration of sublingual nitroglycerin is used. Due to autonomic nervous system disequilibrium during positive HUT, this test has a theoretical arrhythmogenic potential. Methods: In order to test this hypothesis, we analysed the HUT in 2000 consecutively tested patients. None of these patients received cardiac, antihypertensive or any other drug that might influence cardiac function. The overall duration of HUT was 60 minutes and the tilting angle was 60 degrees. 1000 of them received nitroglycerin in the 30th minute (group A), 1000 of them did not (group B).

The orthostatic response in Familial Dysautonomia Hilz MJ, Brown CM, Welsch G, Stemper B, Brys M, Axelrod FB Dept of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany Purpose of the Study: Patients with Familial Dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the etiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate vascular responses to postural stress in FD patients. Methods: Nine FD patients and eleven control subjects had measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO) by impedance cardiography, and calf volume changes by impedance plethysmography while supine and during head-up tilt. During lowering of the legs, we also assessed the venoarteriolar reflex (VAR) by measuring skin blood flow at the dorsum of the foot. Results: Head-up tilting for 10 min induced sustained falls in mean arterial pressure in the FD patients but not in the controls. Total peripheral resistance (TPR, mean arterial pressure/CO) increased significantly in the controls (+ 39.8 ± 6.8 %) but not in the FD patients. Calf volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62 ± 1.99 ml/100 ml) and the controls (3.18 ± 0.74 ml/100 ml). The venoarteriolar reflex was present in the patients (47.7 ± 9 % decrease in skin blood flow) but was impaired as compared with the controls (80.7 ± 3.4 %) (P < 0.05). Conclusion: The impaired VAR and absent increase of TPR confirm that orthostatic hypotension in FD is primarily due to a lack of sympathetically-mediated vasoconstriction but without evidence of abnormally large shifts in blood volume towards the legs during orthostasis.

Risk stratification of patients after myocardial infarction by fuzzy approach N. Honzíková, B. Semrád*, R. Lábrová*, J. Hrabec+, P. Honzík+ Dept. of Physiology and *Dept. of Internal Medicine, Masaryk University, Brno, and +Dept.of Control and Instrumentation, Brno University of Technology, Brno, Czech Rep. Purpose of the Study: Patients (pts) surviving myocardial infarction (MI) are at risk of cardiac death. Indices such as ventricular ectopies per hour (VPCs) > 10; ejection fraction (EF) < 40 %; positive late potentials (LP); baroreflex sensitivity (BRS) < 3 ms/mmHg,SDNNin-

3rd Int. Workshop on Noninvasive Monitoring

dex < 30 ms and SDANN < 50 ms are used for risk prediction, but their predictive value is insufficient. Methods: Fuzzy approach takes into account that the border between a risky and non-risky value of a risk factor is not sharp. Sharp limits of critical values (c. v.) of factors were replaced by linear transitions between 0 and 1. Weighted approach based on Bubble sort method was used for rating a predicting quality of each risk factor. A sum of fuzzified values of risk factors was introduced as a new risk factor. We examined EF by echocardiogram, VPCs, SDNNindex, SDANN from 24-hour ECG, BRS by spectral analysis of blood pressure recording (Finapres), and LP in 290 pts 7–21 days after MI; 18 pts died within 2 years. Sensitivity (Se), specificity (Sp) and positive predictive value (PPV) were determined for standard and for fuzzy c. v. C. v. of summarized risk factors (r. f.) – summa r. f. or summa fuzzy r. f. – were determined: 1.for optimal achievable Se and Sp; 2. for PPV 50 %. Also the predictive value of newly summarized factors were evaluated. Results: Optimal widths of fuzzy sets were 5 % for EF, 3.5 ms/mmHg for BRS, 21 ms for SDANN, 7 ms for SDNNindex and 2.5 VPCs/h. The following predictive values were found: 1.for standard/optimal c. v.: summa r. f. – (c. v.; Se%; Sp%; PPV% – 1; 83.3; 75.7; 18.5), summa fuzzy r. f. (1.2; 83.3; 78.6; 20.5); 2. for PPV 50 %:summa r. f. – (c. v.; Se%; Sp% – 3; 38.9; 97.4), summa fuzzy r. f. –(2.15; 44.4; 97.1). Conclusion: The fuzzy method improved the predictive accuracy of standard risk factors.

Baroreflex sensitivity and heart rate variability in patients with chronic ischemic heart disease and systolic dysfunction: effect of exercise training Jancˇík J, Siegelová J, Svaèinová H, Dobsˇák P, Placheta Z, Fisˇer B, Dusˇek J,Várnayova L.,Vohlídalova I., Panovsky´ R, Meluzín J, * Savin E, *Martineaud JP Medical Faculty, Masaryk University, Brno, CZ, * Hopital Lariboisiere, Paris, France Purpose of the Study: The present study was designed to evaluate whether a specific program of exercise training at anaerobic threshold level may be sufficient to improve BRS and HRV of patients with chronic coronary disease and systolic dysfunction (CCD-SF). Methods: We examined 26 patients with chronic coronary artery disease (cardiography, coronarography) NYHA I-II, stable therapy, body weight of 80 ± 6 kg, age 62 ± 10 years, EF 35 ± 5 %).A symptomlimited spiroergometry was done before and after the training (maximal attained work load Wmax, peak VO2/kg, MET),which consisted of an 8-week long intensive aerobic training (at anaerobic threshold level, 20 min three times a week). BRS was determined by spectral analysis of pulse interval (PI), systolic blood pressure (SBP) (5 minutes of beat-to-beat non-invasive monitoring of blood pressure – Finapres Ohmeda, metronome-controlled breathing 0.3 Hz) before and after the training as well as HRV (Varia Puls T3). Results: The results of PI (ms), SBP (mmHg), DBP (mmHg), BRS (ms.mmHg-1), Wmax (W), peak VO2 (ml.min-1.kg-)and MET are given in the table (mean ± SD) before (B) and after the training. The results of HRV (total power TP ms2, LF 0.04–0.14Hz, HF 0.15–04 Hz, LF/HF) in table (mean ± SD) before (B) and after the training. Conclusions: Significant differences in PI, BRS (2.8 ± 0.8, 3.9 ± 1.0) Wmax,VO2, MET (5.3 ± 1, 6.0 ± 1.4), TP and HF were found (p < 0.05, Wilcoxon). Conclusion: It is concluded that 8 weeks of exercise training at anaerobic threshold level increased pulse interval, baroreflex sensitivity, heart rate variability and maximal attainable work load in patients with coronary artery disease and systolic dysfunction. IGA MZ CR 4705–3, CEZJ037/98:141100004

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Noninvasive analysis of the heart beat and its chronobiological significance Thomas Kenner, Max Moser Physiologisches Institut der Universität Graz, Institut für Nichtinvasive Diagnostik, Weiz Purpose of the Study: The generators of internal rhythms are called pacemakers or internal clocks. Systems with periodic functions are oscillators. Different stimuli from the environment influence the internal rhythms. In particular with respect to circadian rhythms, we speak of “Zeitgeber”. Physiological pacemakers act through the interaction between leaking membrane channels and an enzyme-controlled all-or-none process. The mechanism of the circadian pacemaker in the hypothalamus is based on interaction between the expression of clock-proteins and their delayed inhibiting feedback effect to the corresponding clock-genes. The heart beat expresses the interaction between a surprising number of internal biological and a variety of external rhythms. There are three important phenomena which are of particular interest. 1) Oscillations of biological variables appear to be essential for the efficacy of control. 2) Biological oscillators tend to synchronize. 3) Biological variables in animals of different size, can be expressed statistically as so-called “allometric” functions of the body mass.Among other examples time periods of heart beat and the breath-to-breath periods are longer in larger animals. Methods: We apply an EKG-based noninvasive technique for longterm recording for the analysis of the heart beat, the frequency spectrum of the heart rate, its synchronization with other rhythms, the circadian variations, including sleep, and the effect of stress and rehabilitation. Since the human eye is especially sensitive to colors, we display the results in color-coded form. We supplement our results with data from other authors, especially Halberg and coworkers. Conclusion: We consider that our approach could supplement the noninvasive haemodynamic beat to beat recording of all cardiovascular parameters developed by Skrabal, Fortin and others. (Task Force Monitor, CNSystem, Austria) Supported by the FWF: SFB Optimierung und Kontrolle

Heart rate variability analysis during dynamic exercise M. J. Lewis, M. Kingsley University of Wales Swansea Purpose of study: Three bandwidths are of primary importance in heart rate variability (HRV) analysis of adults during normal activity: (i) VLF, = 0.04 Hz, (ii) LF, 0.04–0.15 Hz and (iii) HF, 0.15–0.4 Hz. The validity of the LF/HF power ratio as an index of autonomic control is uncertain during physical activity. The present study sought to characterise HRV during progressive and intermittent exercise and thus to investigate the optimal choice of HF bandwidth during these conditions. Methods: Seven asymptomatic males were investigated continuously during 5 stages: (1) pre-exercise, (2) progressive maximal exercise, (3) recovery, (4) intermittent exercise (5) recovery. Stage 2 consisted of 3-min cycling stages. Stage 4 consisted of 6-min exercise bouts with recovery (5–1 min). Ambulatory ECG and respiratory parameters were recorded. The power distribution of the HRV signal was analysed within the following bandwidths: 0.02–0.15 Hz (LF), 0.15–0.4 Hz (HF0.4), 0.15–0.9 Hz (HF0.9) and 0.15–2.0 Hz (HF2.0). Results: Differences were observed in the relative changes of power within the HF0.4, HF0.9 and HF2.0 bands during exercise. Exercise caused a rapid reduction in power within the HF0.4, HF0.9 and LF bands. Power within the HF2.0 band increased during stage 2. The central frequency in the HF2.0 band reflected the respiratory frequency. During stage 4, the extent to which pre-exercise total power recovered was dependent on recovery time.

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Conclusion: When assessing the LF/HF ratio during exercise it might be more appropriate to use either the HF0.9 or HF2.0 bandwidths. The wider HF bands ensure the inclusion of the high frequency components that are associated with the increased respiratory activity during exercise.

Effects of dynamic exercise on baroreceptor sensitivity and haemeodynamics

However, this analysis is applicable only for 14 % of the data available with appropriate premature beats and normal beats before and after the arrhythmia. To discriminate between DCM patients and controls, the stepwise discriminant function analysis for all calculated parameters was applied. In this way, a classification rate of 88 % could be obtained for the subgroups with arrhythmias (9 DCM vs. 19 controls, 6 parameters). Conclusion: Using the same amount of parameters in the complete data set (37 DCM vs. 167 controls), a classification rate of 86.3 % was calculated.

M. J. Lewis, M. Kingsley, A. Short, K. Simpson and R. Marson University of Wales Swansea Purpose of study: There have been relatively few investigations into the effects of static or dynamic exercise on beat-to-beat blood pressure and baroreceptor-mediated control of heart rate. This study will investigate the effects of exercise and posture on these parameters, according to the following null hypotheses (H0): H01: Baroreceptor reflex sensitivity (BRS), the set-point (SP) of baroreceptor control and heart rate variability (HRV) will not change at any stage during a progressive intensity exercise protocol. H02: A progressive intensity exercise protocol will have no effect on post-exercise BRS, SP or HRV. H03: Neither BRS nor SP will differ between head-up tilt manoeuvres performed pre- and post-exercise. Methods: The subjects will include 12 male volunteers, in two age ranges: 18–21 years, and > 35 years. Beat-to-beat blood pressure (BP), RR interval, cardiac output and total peripheral resistance will be monitored (Task Force Haemodynamic Monitor, APC Cardiovascular, UK) continuously during the following protocol: 15-min supine; tilt to vertical position; 5-min standing; progressive sub-maximal exercise; 5-min standing/recovery; 15-min supine; tilt to vertical position. Subjects will complete two trials (cycle ergometer and treadmill), following an overnight fast and under controlled laboratory conditions. BP and RR interval variability (HRV) will be investigated in the time and frequency domains, and indices of BRS and SP will be quantified. Conclusion: The study will help to elucidate the nature of the baroreceptor reflex as well as changes in haemodynamic parameters during quantified levels of exercise. This information has potential implications for both clinical assessment and exercise prescription.

Heart rate turbulence versus variability and baroreceptor sensitivity in patients with dilated cardiomyopathy Hagen Malberg1, Robert Bauernschmitt2, Udo Meyerfeldt3, Alexander Schirdewan3, Niels Wessel3, 4 1 Forschungszentrum Karlsruhe GmbH (Karlsruhe Research Center); 2 German Heart Center Munich; 3 Franz-Volhard-Hospital, Berlin; 4 University of Potsdam Purpose of the Study: This study investigated the ability of heart rate turbulence parameters to characterize the regulatory differences in patients with dilated cardiomyopathy (DCM) and healthy controls in terms of heart rate and blood pressure variability as well as baroreceptor sensitivity. Methods and Results: In this study, data from 37 DCM patients and 167 controls were analysed. Using a newly developed heart rate-blood pressure trigger for detecting arrhythmias, premature beats were found in 24.3 % of the DCM patients and in 11.3 % of the controls. The heart rate turbulence shows significant differences in the subgroup of DCM patients and controls with arrhythmias (Turbulence Onset: DCM: 1.80 ± 2.72, Controls: –4.34 ± 3.10, p < 0.001; Turbulence Slope: DCM: 6.75 ± 5.50, Controls: 21.30 ± 17.72, p = 0.021).

Presence of a power spectrum in variability of intraocular pressure in the anaesthesized rat Marques-Neves C, Martins-Baptista Rocha I, Delgado E, Boto JP, SilvaCarvalho L Instituto de Fisiologia, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, 1649–028 Lisbon, Portugal Purpose of the Study: The influence of the autonomic nervous system (ANS) on intra-ocular pressure (IOP) has been known for a long time. In the cardiovascular system the influence of ANS can be revealed by the analysis of heart rate and blood pressure variability. Recently, the presence of harmonics in short time records of IOP was demonstrated. In the present work we tested the hypothesis that the influence of the ANS can be translated into the existence of a power spectrum of variability of IOP. Methods: Experiments were performed on six rats anesthesized with chloralose, paralyzed and artificially ventilated. ECG, arterial blood pressure (BP) (via a cannula inserted into the femoral artery) and IOP (via a needle inserted into the corpus vitreum and connected to a transducer) were recorded. Variables were analysed in respect to frequency domains, using FFT for 5 minutes of recording of stabilized conditions. Atropine was applied to the eye and 5 minutes of recording were repeated. Results: Our results show the presence of three bands on the Power Spectrum of IOP with high correlation to those observed in the systolic blood pressure and heart rate. The HF (high frequency band) is decreased by atropine, thus documenting the parasympathetic influence. Conclusion: These results suggest that the ANS influence on IOP can be evaluated by power spectrum analysis.

Ventricular repolarization in patients with Parkinson’s disease and autonomic dysfunction Meglicˇ B*, Avbelj V**, Trobec R**, Sˇvigelj V*,Mesec A* * University Medical Center, Zalosˇka 7, 1525 Ljubljana, Slovenia; ** Jozef Stefan Institute, Jamova 1, 1000 Ljubljana, Slovenia Purpose of the Study: Cardiac autonomic denervation present in patients with Parkinson’s disease might influence ventricular repolarization. The aim of the study was to evaluate ventricular repolarization in patients with Parkinson’s disease and dysfunction of the autonomic nervous system (ANS). Methods: Twenty patients with Parkinson’s disease and cardiovacular autonomic dysfunction and twenty age- and sex-matched controls were included in the study. High resolution ECG was recorded for 5 minutes under standardized conditions in every individual and analysis was performed off-line. RR interval and temporal QT interval length and variability were calculated. Spectral analysis of both RR and QT interval series were performed and the power of spectra in low (0,04–0,15 Hz) and high (0,15–0,4 Hz) frequency bands was calculated.

3rd Int. Workshop on Noninvasive Monitoring

Results: Patients had significantly decreased RR variability and increased QT variability (p < 0,001 and p < 0,05, respectively). While RR interval variability was decreased in both low and high frequency spectral bands, QT interval variability was increased in high and decreased in low frequency bands. Coherence between RR and QT spectra was lower in both frequency bands in patients, but the difference did not reach statistical significance. Conclusion: Patients with Parkinson’s disease and autonomic dysfunction have increased temporal dispersion of ventricular repolarization. The direct, heart rate independent autonomic regulation of ventricular repolarization might be disturbed in such patients.

Nonlinear analysis of heart rate variability and other parameters of autonomic dysfunction in risk stratification of patients with myocardial infarction B. Milovanovic, M. Krotin, S. Kulezic, A. Milovanovic, V. Bisenic C. H. C. B. Kosa Department of Cardiology, University of Belgrade, Yugoslavia; Bezanijska Kosa b. b.11080 Zemun, Belgrade Purpose of the Study: It is a well known fact that analysis of heart rate variability in combination with other parameters, especially ejection fraction, is a very useful method for risk-stratification of patients with myocardial infarction. The aim was to evaluate space plots of nonlinear parameters of HRV and other risk predictors related to the function of the autonomic nervous system by visual inspection. Methods: We studied 590 patients with myocardial infarction, using additional methods and tests after the onset of myocardial infarction. All patients underwent short term (5min) (1st and 3rd week) and long term ECG-analysis (Holter-ECG) (3rd week) for heart rate variability, QTc- interval and -dispersion (1st, 7th day, 3rd week) and late potentials (1st, 7th day, 3rd week). Echocardiography for the detection of systolic (EF < 40 %) and diastolic (A > E) disorders was also carried out.The results of nonlinear analysis were categorized according to the visual form (“cigarette”,“cluster”,“comet”) of the space plots. Results: Patients with systolic heart failure had space plots in the shape of a cigarette (n = 41, 59.4 %), a comet-like plot in 16 pts. (23,2 %) and a cluster-plot in 12 pts. (17.4 %) (p < 0,05).The patients with space plots in the shape of cigarette a had higher values of their QTc-intervals (p < 0,05). Late potentials were present in 21(77,80 %) patients with space plots as a cigarette, in 4 patients (14,8 %) with comet-plots and in 2 patients (7,4 %) with cluster-plots (p < 0.05). Of the patients with ventricular tachycardia (VT), 14 (77.8 %) had cigarette-plots, 3 (16.7 %) had comet-plots and 1 (5.6 %) had a cluster-plot (p < 0.01). Conclusion: In patients with space plots of cigarette-shape there was an increased frequency of VT, positive late potentials and systolic dysfunction of higher degree.

Nonivasive markers of the cardiovascular autonomic regulation – review of methods and the author’s own observations Tadeusz Nawarycz, L Ostrowska-Nawarycz J Blaszczyk Department of Human Physiology and Biophysics, Medical University, Lodz, Poland Purpose of the Study: Disturbances in vegetative regulation of cardiovascular system area have a subclinical character and usually are the first symptoms of the disease. The recent achievements in the area of non-invasive diagnostics of cardiovascular system neuroregulation have been reviewed. New means of examining the vegetative system with the use of the below methods of analysis are being presented:

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1 heart rate variabilities (HRV) in different domains (time, frequency and nonlinearity domains), 2 heart rate turbulence (HRT), 3 baroreceptor sensitivity (BRS) and 4 electrodermal activity (EDA). Methods: Diagnostic and practical applications of the above mentioned methods are being presented.We also describe selected methods of advanced biomedical signal processing: 1 wavelet analysis methods (analysis of HRV signals), 2 artificial neuronal networks (classification of signal frequencies). Results and conclusions: On the basis of the authors’ own experience and the data presented in the pertinent literature, the authors arrive at the following major lines of research: 1 Elaboration of a precise biophysical model of the circulatoy system with consideration of various mechanisms of autonomic regulation in regard to different function tests; 2 Evaluation of an integral efficiency-coefficient of autonomic cardiovascular regulation mechanisms; 3 Elaboration of an automatic classification of autonomic regulation dysfunction; and 4 Application of new methods of analysis and signal processing

Peripheral arterial tonometry reflects autonomic changes in patients with sleep related breathing disorders T. Penzel, I. Pinnow, H. F. Becker, C. F. Vogelmeier Klinik für Innere Medizin, Klinikum der Philipps-Universität, Marburg, Deutschland Purpose of the Study: Sleep apnea and sleep related breathing disorders have been recognized as an important risk factor for cardiovascular disorders. Therefore the diagnosis of obstructive sleep apnea requires the assessment of cardiovascular function. Recently, a new sensor had been introduced which monitors autonomous nervous function by the measurement of peripheral arterial tone (PAT) on the finger. This sensor follows finger volume changes which accompany the pulse wave. In order to relate these changes to the cardiovascular effects of sleep apnea we compared PAT with invasive blood pressure during sleep. Methods: Twentyone patients with obstructive sleep apnea and arterial hypertension underwent polysomnography with parallel invasive blood pressure and PAT. All signals were recorded digitally to allow later data processing. Results: The PAT-signal follows the hemodynamic changes during each apnea in a complex way. During the initial phase of the respiratory cessation, the PAT signal amplitude increases. The amplitude reaches its maximum at the end of the apnea. The signal amplitude attenuates strongly during the apnea terminating central nervous arousal. The attenuation reflects the autonomic change at the end of each apnea. This can be used to detect apneas. Correlation between PAT attenuations and cortical arousal was significant (r = 0.583; p < 0.01); between apnea and hypopnea events r = 0.656 (p < 0.01) was even higher. Conclusion: The PAT-signal cannot replace invasive BP measurements, but provides additional information which allows to investigate changes of sympathetic and parasympathetic activities during sleep. The attenuations of the PAT-signal are good enough to detect arousal and apnea events. Based on this, an ambulatory PAT recorder was developed and tested for the detection of sleep related breathing disorders.

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A new method to estimate baroreflex sensitivity by using the TRS-technique in short data segments. H Ruediger, M Bald, K Scheuch, M Krause Dresden University of Technology, Germany, Institute of Occupational and Social Medicine Purpose of the Study: The underlying concept of this new method is the statistical dependence between spontaneous fluctuations of systolic blood pressure (SBP) and RR-intervals to estimate baroreflex sensitivity (BRS) in short data segments. Blood pressure and R-R intervals responses to vasoactive drugs have been most widely used to estimate the BRS, but this invasive method is limited in use. Therefore, mathematically valid non-invasive methods are of particular importance. One of the most frequently used non-invasive algorithms is the sequence technique. Methods: The empirical data set is sampled to identify three or four consecutive beats characterized by a progressive increase/decrease in SBP (increasing/decreasing BP ramps).This technique requires, however, long data segments (10 to 15 minutes).An alternative approach is the estimation of linear regression of the BRS, not on the basis of increasing or decreasing empirical sequences but on the basis of physiological oscillations, which represent the empirical measurements statistically. Results and conclusions: The TRS-technique [1] is able to find out such oscillations. A comparative study of both methods in children and young adults is given in [2]. A comparison of both methods by Bland and Altman showed a very good correspondence with a high correlation (r ≥ 0.9). The time segments used are two minutes. References 1. Ruediger H, Klinghammer L, Scheuch K (1999) The trigonometric regressive spectral analysis – a method for mapping of beatto-beat recorded cardiovascular parameters onto frequency domain in comparison with Fourier transformation. Comput Methods Programs Biomed 58:1–15 2. Ruediger H, Bald M (2001) Spontaneous baroreflex sensitivity in children and young adults calculated in the time and frequency domain. Autonomic Neuroscience: Basic & Clinical 93:71–78

Cardiovascular regulation to mental stress in normotensive and hypotensive women Reingard Seibt, Stefan Weigel, Heinz Ruediger University of Technology Dresden, Germany, Institute of Occupational and Social Medicine Objective: A very low blood pressure (BP) is a sign of a disturbed sympatho-vagal balance in hypotensive subject. The heart rate (HR) variability (HRV) has been examined to reveal whether normotensive and hypotensive subjects differ with respect to their sympatho-vagal balance under rest and mental load. Methods: The cardiovascular regulation (fixed sequence: habituation, two mental tests, recovery) was compared in fifty hypotensives (BP: 101/62 mmHg; HR: 73 bpm) and 50 normotensives (BP: 120/72 mmHg; HR: 76 bpm) under standardized laboratory conditions. Additional to the brachial BP (Riva-Rocci), the peripheral BP (Finapres) and the HR were continuously recorded. For analyses of HRV the trigonometric regressive spectral analysis was used. The mean variance part [%] and the mean LF/HF-ratio were computed for the very low (VLF:.003–0.04 Hz, the low (LF:.04–0.15 Hz), and the high frequency band (HF:.15–0.40 Hz). Results: For all laboratory conditions, the mean values of brachial BP and HR were significantly lower in HY than in normotensives. Mental load was found to increase BP and HR in both groups, but the

reactivity of brachial BP and HR was found to be significantly smaller in hypotensives. No differences between both groups were found in peripheral BP under mental load. In hypotensives the spectral analysis revealed a lower variance part in the LF-band and a higher one in the HF-band (reduced sympathetic and an increased parasympathetic activity). The LF/HF-ratio was significantly increased in normotensives. The mean variance part in LF-band showed a significant increase under mental stress in both groups. Conclusion: These findings demonstrate a parasympathetic predominance in HY in contrast to NO, and the activation of the cardiovascular system is smaller under mental load in hypotensive as compared to normotensive subjects.

Predictive value of heart rate variability for the presence of sleep apnoea Seyfert H., Wendt Th. Rehabilitations-Klinik Wetterau der BfA, Zanderstr. 30–32, D-61231 Bad Nauheim Purpose of the Study: Does non-simultaneous analysis of heart rate variability obtained by Holter-monitoring reliably indicate the presence of a sleep related breathing disorder in comparison with Polymesam-screening? Methods: 120 consecutive patients were analysed with Polymesam for the presence of sleep apnoea. The results were compared with those of a non-simultaneously registered Holter-monitoring supplying heart rate variability data. Sensitivity and specificity of heart-rate variability for a pathologic sleep apnoea screening were calculated. Results: When setting the cuttoff-line for a normal rdi at < 10 and for a pathologic rdi at > = 20, heart rate variability data for SDNN-i were 50,77 ± 2,67 vs 61,07 ± 3,88, TF 54,12 ± 2,67 vs 68,87 ± 5,48, and 42,59 ± 2,04 vs 52,17 ± 3,05, respectively. Heart rate analysis had a sensitivity of 51,5 % and a specificity of 70,8 % for predicting a pathologic rdi using values of 61,07 ms for SDNN-i, 68,87 ms for TF and 52,17 for VLF as combined criteria. Correlation between SDNN-i, TF, VLF, and RDI were significant (p < 0,01) but correlation-coefficients were only fair (0,2526, 0,2775, and 0,2554, respectively). Conclusion: Heart rate variability can indicate the presence of sleep apnoea with low sensitivity but with adequate specificity. The results obtained by non-simultaneous registration do differ to a certain degree from those obtained by simultaneous registration by placing emphasis on SDNN-i, TF, and VLF instead of rMSSD, pNN50, and HF as reported in the literature.

Blood pressure and heart rate monitoring in humans: the circaseptan and circadian rhythms J. Siegelová, G. Cornélissen, B. Fisˇer, J. Dusˇek, P. Homolka, M. Masˇek, J. Janèík, H. Svaèinová, F. Halberg Dept. of Functional Investigations and Rehabilitation, St.Anna Teaching Hospital, Medical Faculty, Masaryk University, Brno, Cz, and The Halberg Chronobiology Center Purpose of the Study: Neonatal c-v.-monitoring of the circadian pattern of heart rate (HR) and blood pressure (BP) was shown by Halberg et al. (1986), Kellerova (1985), Hellbrugge (1960) and others.The aim of this study was to analyse BP and HR in newborns and adults and study the circaseptan and circadian variability. Methods: Long-lasting BP and HR monitoring was applied using an oscillometric sphygmomanometer automatically every 30 minutes in 86 premature babies.The 86 premature babies (850 to 3250 g. b.w) were seriously ill, 27 of them died later, 12 of them were diagnosed as having intracranial hemorrhage. The values of systolic BP (SBP), di-

3rd Int. Workshop on Noninvasive Monitoring

astolic BP (DBP) and HR were analysed using the computations of spectral analysis and Halberg’s cosinor analysis. Seven-day lasting blood pressure monitoring was analysed in 145 adults from the Brno district using an oscillometric device (Japan). Results: Slow significant oscillations (p < 0.05) with a different period between 5 to 10 days (an about-weekly component, circaseptan) were found either in HR, SBP or DBP in all newborn babies (100 %). The significant peak of circadian rhythm (p < 0.05) was found in HR in 50 % of premature newborn babies, in SBP or DBP only in 43 %. Cosinor analysis showed that circaseptan rhythms are more prominent in blood pressure and heart rate than the circadian rhythms. Our results showed that the circaseptan rhythms in BP and HR rate are independent of the week days and that the origin of the circaseptan rhythm is dependent on the time of birth in newborns. The least squares spectra from 145 subjects showed the significant circadian rhythm in SBP, DBP and HR, the amplitude for SBP was 9.54 mmHg, DBP 7.25 mmHg, HR 7.25 bpm. Conclusion: The circaseptan period was statistically significant for SBP, but not for DBP and HR. Support: CEZ J037/98:141100004

Cardiovascular responses to apnea and exercise Smerecnik, Mirco; Hoffmann, Uwe; Leyk, Dieter Department of Physiology, Deutsche Sporthochschule Koeln, Cologne, Germany Purpose of the Study: We sought to investigate cardiovascular responses to breath holding and rebreathing combined with intensive dynamic exercise. Breath-holding for several seconds frequently occurs in several sports activities. It is hypothesized that the baroreflex to apnea,combined with exercise and the Valsalva maneuvre, mediates the response of heart rate (HR) and mean arterial blood pressure (MAP). As a consequence of these combined stresses, different and competing physiological reflexes and regulatory processes are activated. Methods: In the first series we tested 16 healthy sports students who performed 20sec of bicycle exercise at 250 W/60 rpm combined with apnea (A&P250W) and 20 mmHg mouth piece pressure (MPP), free breathing (P250W) and apnea with a workload of 30 W (A30W) in supine position, all preceded by 280 sec of 30W/60 rpm pedalling. In the second series we tested 12 subjects; we modified the first series and replaced apnea by rebreathing (RB250W, RB30). The breathing valve was under subjects’ control, mouth piece pressure (MPP) and pedaling frequency were continuously signaled to the volunteer on a LCD. HR and MAP were continuously recorded. Results: We observed a marked fall in HR and an increase in MAP in the last 5 sec during the 20 sec apnea period (A&P250W). In the rebreathing experiment, we observed stabilisation of the HR but no remarkable increase of MAP. Conclusion: We conclude that breath-holding is the significant stimulus,which is superimposed on the exercise stimulus for HR and MAP.The maintained breathing movements during rebreathing attenuate the bradycardia and the MAP implying that the cardiovascular response seems to be more determined by the respiratory arrest. However,a chemoreceptor-controlled O2-conserving mechanism during apnea seems to have a subordinate role.

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Baroreflex sensitivity in patients with diabetes mellitus and essential hypertension 1

Svacinova H, 1 Siegelova J, 1 Fisˇer B, 1 Dusˇek J, 1 Svoboda L., 1 Jancik J, 2 Olsovsky J, 2 Zackova V 1 Dept of Functional Diagnostics and Rehabilitation; 2 Second Dept of Internal Medicine, Faculty of Medicine, Masaryk University Brno, St.Anna’s University Hospital, CZ Purpose of the Study: The evaluation of the effect of pharmacological and non-pharmacological therapy on baroreflex sensitivity (BRS) on the heart rate in patients with diabetes mellitus type 2 (DM) and essential hypertension (EH). Methods: In two groups of DM with hypertension (ACE inhibitors or Ca-channel blockers, DMH, n = 7, age 56 ± 4 years) and without hypertension (DMN, n = 6, age 60 ± 8 years), BRS was evaluated before (1) and after (2) 12 weeks of a walking training program. BRS was measured in patients with essential hypertension (EH, n = 11, age 60 ± 6 years), in normotensives (N, n = 11, age 58 ± 6 years), in patients with EH and monotherapy (ACE inhibitors or Ca-channel blockers, EHT1, n = 12, age 59 ± 6 years) and in EH with combined therapy (EHT2, n = 18, age 48 ± 5 years). BRS was determined by spectral analysis of spontaneous fluctuations of systolic blood pressure (SBP) and cardiac intervals (CI) (Finapres, 5 min record, metronome-controlled breathing at frequency 0.33 Hz). Statistical analysis of data: Wilcoxon paired test and ANOVA; a p < 0.05 was considered significant. Results: as mean ± SD are given in Table 1. Conclusion: BRS was significantly increased after 12 weeks of a walking training program in diabetics without hypertension as well as in diabetics with hypertension controlled by monotherapy (p < 0.05). The value of BRS in normotensives (N) corresponds to the values of BRS in the diabetics with hypertension after training (DMH2) as well as to patients with essential hypertension with combined pharmacotherapy (EHT2). Support:CEZJ037/98:141100004

Baroreflex chronotropic reaction amplitude is age – and baseline heart rate – dependent Vitols A, Voita D Latvian Institute of Cardiology, Riga, Latvia Purpose of the Study: To assess the effect of a subject’s age and baseline heart rate on baroreflex chronotropic reaction amplitude, which is widely used as a measure of baroreflex sensitivity. Methods: In group of 51 healthy subjects (F- 28; M- 23; age range from 18 to 56 years), the amplitude of the bradycardic reaction to carotid baroreflex-activation by neck-suction (–50 mmHg for 5 s) was analysed. Beat-to-beat heart rate values and mean arterial finger pressure was monitored continuously by Physiograph UT-8506. The difference between the lowest heart rate value during the neck suction and the value immediately before suction was taken as the bradycardic reaction. The mean of 6 measurements was calculated. Results: In healthy subjects, the bradycardic and hypotensive reactions to carotid baroreflex activation at rest were individually different, but they were stable for each particular subject during the considered time period. Bradycardic reaction amplitude decreased with increasing age of the subject (r = –0.64; P < 0.01). In different age sub-

Table 1 To Baroreflex sensitivity in patients with diabetes mellitus and essential hypertension

BRS(ms/mmHg)

DMN1

DMN2

DMH1

DMH2

EH

N

EHT1

EHT2

3.1±1.1

4.7±1.2

5.1±1.8

7.2±2.3

4.7±1.8

7.8±3.8

4.9±2.7

8.2±3.4

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groups (A, mean age 24 + 0.8 yrs; B, 35 + 0.7 yrs; and C, 46 + 0.9 yrs), the bradycardic reaction amplitudes were 14 + 0.8 bpm; 11.7 + 0.6 bpm; 8.1 + 0.4 bpm, respectively (A vs.C; P < 0.05); the baseline heart rates were 74 + 1.6 bpm; 73 + 1.6 bpm; 63 + 1.7 bpm, respectively (A vs.C P < 0.05). At the same time, bradycardic reaction amplitude was inversely related (r = –0.66; P < 0.05) to baseline heart rate increase (caused by the orientation reaction to the study procedure); however,the disappearance of this reaction is followed by an increase of the bradycardic reaction amplitude. Conclusion: Baroreflex chronotropic reaction amplitude is related to subject age and modified by autonomic neural drive affecting heart rate.

Baroreflex sensitivity and blood pressure variability in hypertensive adolescents E. Závodná, P. Lokaj, Z. Nováková, J. Padeˇrová*, P. Václavková*, H.Hrstková*, N. Honzíková Department of Physiology and *Department of Paediatrics, Faculty of Medicine, Masaryk University, Brno, Czech Republic Purpose of the Study: The aim of the present study was to determine differences in baroreflex regulation of circulation between hypertensive and healthy adolescents. Methods: We examined 102 adolescents (16–19 years): 86 healthy controls (Co) and 16 adolescents with hypertension (Hy). Systolic blood pressure (SBP) and pulse intervals (PI) were recorded for 5 min (Finapres, metronome-controlled breathing at a frequency of 0.33 Hz). The index of baroreflex sensitivity (BRS) [ms/mmHg] was determined by spectral method. The SBP and PI variability were determined as spectral power in the range of the 10-second rhythm (varSBP, varPI). Adolescents were divided into groups according to the BRS: low 1–5.79 ms/mmHg (lBRS), mean 5.8–12.79 ms/mmHg (mBRS), more than 12.8 ms/mmHg (hBRS). Results: Besides higher SBP (p < 0.01), the Hy youths had lower BRS (p < 0.01), higher varSBP (p < 0.01), weight (p < 0.01) and BMI (p < 0.01) than Co. In group lBRS, Hy compared with Co had higher weight (p < 0.01) and BMI (p < 0.01). In group mBRS, Hy vs. Co had higher varSBP (p < 0.01) and varPI (p < 0.01). There were 24 Co and no Hy in group hBRS. Conclusion: An increased SBP in adolescents is associated with overweight. BRS is decreased in Hy adolescents.In the group with low BRS,the dampening effect of BRS on varSBP is insufficient in both Hy and Co. In the group with medium level of BRS, Hy had significantly higher SBP variability.This could be a sign of increased sympathetic vasomotor activity. Supported by grant CEZ: J07/98:141100004.

Haemodynamics Cardiac output by model flow method from intra-arterial and pulse pressure profiles Azabji KM*, Lador F*, Moia C*, Morel D†, Ferretti G* * Department of Physiology, University Medical Centre; † Division of Anesthesiology, Geneva University Hospital, Geneva, Switzerland Purpose of the Study: Pulse contour or model flow (MF) methods of measuring cardiac output (Q) from pulse pressure (PP) profiles recorded non-invasively from the finger tip (FT) are promising, but are adversely affected by the quality of the tracings, since distortion of the pressure profile may occur, especially when finger blood flow is

reduced. A comparison of MF Q data computed from PP tracings simultaneously obtained from FT and from an intra-arterial catheter (IA) on the same subject at rest and exercise was, to our knowledge, not done so far. The aim of this study was to compare beat-by beat Q data with MF method applied to PP profiles obtained from FT and IA Methods: The study was conducted on 7 subjects 24.7±3.2 years old. A catheter carrying a pressure head was inserted in the radial artery. A finger pressure device was placed on the contralateral side for continuous monitoring of non invasive PP. Exercise (10 min at 50 W and 10 min at 100 W) was carried out on a cycle ergometer. The data acquisition was made at a rate of 100 Hz. The obtained PP profiles were analysed for systolic and diastolic blood pressure (Ps and Pd, respectively). Beat-by-beat Q was subsequently computed with the MF method. Results: Ps was 149±14 and 121±14 at rest, 165±13 and 160±18 at 50 W, and 170±14 and 163±22 for IA and FT, respectively. Pd was 86±6 and 71±14 at rest, 87±8 and 78±17 at 50 W, and 86±7 and 76±14 for IA and FT, respectively. Q was 5.7±1.3 and 6.2±2.4 at rest, 9.6±1.4 and 11.5±4.2 at 50 W, and 11.8±1.8 and 13.5±3.6 for IA and FT, respectively. The linear relationship between FT Q and IA Q (y = 1.2419x – 0.5126, R2 = 0.6388) had a slope significantly Higher than 1. Conclusion: We conclude that non-invasive PP profiles obtained with FT provide an overestimate of Q with respect to IA profiles. FT Q requires calibration against an independent Q method.

Root Mean Square Step-down Transformation for dZ/dtmax, and Development of a New Stroke Volume Equation for Impedance Cardiography: Impedance Velocimetry Donald P. Bernstein, M. D. Palomar Medical Center, Escondido, California 92067, USA Purpose of the Study: To determine ohmic mean velocity from ohmic peak acceleration, and a new SV equation. Methods: Critical analysis of the componentry of dZ/dt, its peak magnitude, and time to peak from point B. Results: It is found that the “time-to-peak” of dZ/dtmax from point B is not within the time domain of peak velocity or flow. It was found that the “time-to-peak” of dZ/dt was within the respective time domains of peak aortic blood acceleration, dQ/dtmax, and LVdP/dtmax. In view of the fact that stroke volume (SV) is computed from a mean flow velocity value, dZ/dtmax cannot be used for this purpose. It was found that the square root of dQ/dtmax = Vmax (peak aortic linear velocity). Since the normalized value of dZ/dtmax (dZ/dtmax/Zo) represents the ohmic image of dQ/dtmax, the square root transformation yielded the ohmic equivalent of velocity. Since rho(t) is the ohmic equivalent of the reduced average velocity (Vmean/vessel radius), (d rho(t)/dtmax)^0.5 = rho(t), which is the square root step-down transformation. Since ohmic mean spatial velocity is the result of the transformation, concerns about arterial runoff (dZ/dtmax X LVET) are unfounded. Since dZ/dtmax is the equivalent of d rho(t)/dtmax, (dZ/dtmax/Zo)^0.5 = rho(t)/rho(stat). Since the square root transformation yields numeric equivalents of Vmean which are several magnitudes larger than raw values of dZ/dtmax/Zo, the volume conductor, Vc, is obligatorily smaller. The magnitude of the Vc was found to approximate intrathoracic blood volume, modified for excess EVLW, by the allometric relationship, ([16 (weight)^1.02]/mZt), which yields volume in mL. mZt = modulus of transthoracic specific impedance. Conclusion: The new SV equation is given as: SV = (Vc/mZt) ([dZ/dtmax/Zo]^0.5)(LVET)

3rd Int. Workshop on Noninvasive Monitoring

Perceived Stress and impedance cardiography-derived hemodynamic profile in patients with fibromyalgia Hans C. Friederich, Dieter Schellberg, Knut Mueller, Stephan Zipfel, Wolfgang Eich Internal Medicine and Psychosomatics, University of Heidelberg, Germany Purpose of the Study: Was to test the influence of perceived stress on the hemodynamic response profile among patients with fibromyalgia [FM]. Methods: To address this question, we investigated the relationship between individually perceived stress (PSQ; Fliege et al. 2001) and hemodynamic variables obtained by impedance cardiography (stroke volume [SV], total peripheral resistance [TPR]) obtained at rest and under mental as well as orthostatic stress). 28 women with FM (age: 40–65 years) participated in the exploratory study. Results: Resting hemodynamic variables show no significant association with individual stress perception. Under stress conditions SV and TPR were reciprocally related to perceived stress and show no association with the magnitude of blood pressure. While the PSQ-subscale “demands”, which focuses on the perception of external stressors, shows a predominant association with a myocardial response under orthostatic stress (SV: r = 0,71, p < 0,01; TPR: r = –0,73, p < 0,01), the subscale “worries”, which represents perceived internal stress reactions of the individual, shows a pronounced vascular response under mental stress (SV: r = –0,56, p < 0,01; TPR (r = 0,56, p < 0,01). Conclusion: Our findings suggests that stress perception in patients with fibromyalgia is associated with characteristic changes in hemodynamic profiles under stress. The different patterns of activation (myocardial vs. vascular) between mental and orthostatic stress are related to different dimensions of stress perception (external vs. internal). Further studies are necessary to find out to what extent our findings are applicable to other stress-related disorders and if they are of significance in predicting cardiovascular risk and pathology.

Acute Haemodynamic and Autonomic Changes induced by Dynamic Exercise Gerfried Gratze, Harald Mayer, Jörg Lindenmann, Petra Mächler, Falko Skrabal Krankenhaus Barmherzige Brüder, Teaching Hospital Karl Franzens University, Marschallgasse 12, A-8020 Graz, Austria Purpose of the Study: The acute changes of haemodynamic (especially stroke volume (SV), total peripheral resistance (TPRI)) and of autonomic function induced by dynamic exercise have not been documented in detail due to lack of suitable noninvasive methods. Therefore we have studied sedentary subjects, trained athletes and patients with coronary heart disease during graded dynamic exercise using a bicycle ergometer and the noninvasive Task Force Monitor which provides all haemodynamic and autonomic parameters. Methods: We have performed exercise testing in 41 male subjects and 12 female subjects (age range 20 to 76 years) using the Task Force Monitor, which provides, heart rate, SV, blood pressure (BP), TPRI on a beat to beat basis. In addition the instrument provides power spectra analysis of heart rate (HR) variability (the high frequency band (HF) as indicator of vagal tone) and of BP variability (low frequency band of diastolic BP as indicator of sympathetic drive). 8 subjects were sedentary, 34 were trained athletes (VO2max > 130 %) and 11 patients had coronary heart disease with stable angina. Results: In healthy subjects haemodynamic exercise leads, despite the rise of HR and hence shortening of filling time, to a rise of SV of 23 ± 12 %, the maximum being observed at 100 Watt with no further increase at higher work intensities. Furthermore an immediate fall of TPRI by an average of 31 ± 3.2 % (± SD) already seen at 25 Watt is ob-

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served. TPRI decreases linearly further to 50 ± 2.4 % of the initial value at full workload. Sympathetic drive as measured by the LF band of diastolic BP shows a biphasic pattern: First it increases on average from 40 ± 11nU to 62 ± 9.3nU at 100 Watt, then it declines again to 35 ± 6.3nU at full workload. Parasympathetic tone (HF band of HR interval) shows also a biphasic pattern: Initially it declines from 18 ± 6.4nU to 9 ± 3.1nU at 100 Watt and it increases to 55 ± 17nU at full workload. Patients with coronary heart disease lack the initial rise of SV and show a markedly reduced initial fall of TPRI. Conclusions: The haemodynamic monitoring of exercise testing gives unique insight into the mechanisms involved in the adaptation to dynamic work. So we can demonstrate a rise of stroke volume despite the decreased filling time, probably mediated by the initial increase of sympathetic tone. Furthermore it allows to quantitate the immediate vasodilation induced by exercise which could be a good indicator of endothelial function since it is impaired in patients with coronary heart disease. The changes in autonomic nervous system activity may possibly be suited to assess the training level in athletes.

Comparison of different techniques to measure cardiac output (CO) during hemodialysis (HD) 1

Bernd Haditsch, 2 Peter Wabel, 1 Peter Krisper, 1 Herwig Holzer, Daniel Schneditz 1 Dept of Int Med, Div of Nephrology, University Graz; 2 Fresenius Medical Care, Div of Therapy Concepts, Bad Homburg, Germany; 3 Dept of Physiology, IBMS, Univ Graz 3

Purpose of the Study: CO is an important hemodynamic variable for peripheral resistance and blood pressure stability. Whereas beat-tobeat measurements of arterial blood pressure are well established, the non-invasive measurement of CO still causes considerable difficulties.The aim of this study was to compare different methods of noninvasive CO measurements during HD (saline dilution; aortic flow reconstruction; thoracic impedance cardiography) with indocyanine-green dilution using transcutaneous dye detection. Methods: Ten patients were studied during their regularly scheduled HD treatment. CO was determined during the first (M1) and the last (M2) quarter of each treatment using the saline (CO-HDM, HDM01) and indocyanine-green (CO-ICG, DDG-2001K) dilution methods. During the whole HD session, beat-to-beat CO was modeled by vascular unloading technique and reconstruction of aortic flow using a Windkessel model (CO-FIN, Finometer). In 5 patients CO was also calculated according to Sramek from thoracic bioimpedance data (COZ; CardioScreen) filtered with 200 Hz. Results: At M1, the CO-HDM was 7.35 ± 0.31L/min, whereas CO-ICG was 4.30 ± 0.10L/min. Corresponding CO-FIN (averaged over 30 seconds) was 6.62 ± 0.12L/min. At M2 CO-HDM was 6.89 ± 0.19L/min, CO-ICG was 4.29 ± 0.13L/min and CO-FIN was 5.86 ± 0.10L/min. At M1, CO-Z was 5.26 ± 0.06, and at M2 4.91 ± 0.26L/min, respectively. Conclusion: While all methods produced plausible and reproducible average values for CO, the relationship between different techniques showed a wide scatter. The poor correlation between techiques could be related to the special hemodynamic situation in HD patients characterized by a large arterio-venous shunt which may adversely affect the models used for non-invasive CO-monitoring. Supported by the Austrian Ministry of Science, Education & Art (grant UGP4), and Fresenius Med Care, Germany.

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The Heritabilty of Haemodynamic Variables Contributing to Blood Pressure in a Large Omani Pedigree: First Report of The Nizwa Blood Pressure Study

Enhanced external counterpulsation does not compromise cardiovascular autonomic modulation and cerebral autoregulation

Hassan M.O., Albarwani S., Al Yahaee S., Comuzzie A.G., Bayoum R.A. College of Medicine, Sultan Qaboos University, Muscat, Sultanate of Oman and the Southwest Foundation, San Antonio, Texas, USA

Hilz MJ1, 2, Werner D3, Brown CM2, Neundörfer B2, Daniel WG3, Marthol H1 1 Dept. Of Neurology, New York University, NY, USA; 2 University of Erlangen-Nuremberg; 3 Dept. of Cardiology, University of ErlangenNuremberg, Germany

Purpose of the Study: The aim of this project is to examine the genetic influence on haemodynamic and other related variables contributing to blood pressure in 5 generations of a large Omani pedigree. Methods: In 177 members of one semi-rural Omani family, age 16–90 yrs, R-R interval, heart rate (HR), systolic (SBP), diastolic (DBP), mean blood pressure (MABP), stroke volume (SV) and total peripheral resistance (TPR) were measured non-invasively using the Task Force Monitor which provides continuous beat-to-beat blood pressure and cardiac parameters. Twentyfour-hour ambulatory blood pressure (ABPM, Schiller) was also recorded Haemodynamic variables were measured after 10 minutes of rest and during 3 minutes of mental stress using the Stroop colour test and 3 minutes of foot-immersion in ice. Genetic parameters were estimated using variance decomposition methods implemented in the SOLAR software package. Results: Based on a simple analysis model with age, sex and blood pressure status as covariates, more than half the traits show significant heritability.Variables showing the strongest additive genetic heritability (h2) were resting SV, (h2 = 0.3, SE ± 0.13, P < 0.0009), ice TPR (h2 = 0.40, SE ± 0.15, P < 0.0005) ice SV (h2 = 0.24, SE ± 0.14, P < 0.009), colour TPR reactivity (h2 = 0.25, SE ± 0.14, P < 0.003) and ice DBP (h2 = 0.37, SE ± 2.0, P < 0.002).).ABPM showed a strong heritability only for DBP during daytime activity (h2 = 0.27, SE ± 0.14 P < 0.0071). Conclusion: These preliminary results show that, of the haemodynamic variables, SV and TPR, the main components of BP, are under significant genetic influence in this population. In order to obtain detailed haemodynamic data in a large population, a versatile non-invasive monitors like the TFM seems to be the appropriate tool.

Dynamic autoregulation testing in patients with middle cerebral artery stenosis C. Haubrich MD, W. Kruska, R. R. Diehl PhD, W. Möller-Hartmann MD, C. Klötzsch MD Department of Neurology, University Hospital Aachen, Germany Purpose of the Study: Cross-spectral analysis (CSA) of spontaneous oscillations in cerebral blood flow velocity (CBFV) and blood pressure (BP) is a sensitive and convenient method for dynamic autoregulation testing. CSA has not been used so far in patients with stenosis of the intracranial arteries. Methods: This study applied dynamic autoregulation testing to 26 M1-stenoses of low, moderate and high degree and 14 normal controls. By means of CSA, we studied M-waves 3 to 9 cpm and B-waves 0.5 to 3 cpm in continuous recordings of Transcranial Doppler of the middle cerebral artery and simultaneously recorded beat-to-beat blood pressure. Results: A gradual decrease of pulsatility indices confirmed the increasing hemodynamic relevance of the stenoses. When compared to controls, M-wave phase shifts between CBFV and BP were gradually reduced with increasing degree of M1-stenosis (Controls: 44.6 ± 21.1°; High degree stenosis: 16.7 ± 19.5°). The phase relation between B-waves in peripheral blood pressure and cerebral blood flow velocity was shifted to positive values (Low degree stenosis: –9.7 ± 108.4°; High degree stenosis: 50.9 ± 43.8°). Conclusion: As B- wave oscillations and M-wave phase shifts seem to characterize the degree of autonomy of cerebral blood flow modulation, both results suggest that with increasing degree of M1-stenosis the arteriolar function is impaired.

Purpose of the Study: Enhanced external counterpulsation (EECP) improves coronary perfusion. The diastolic lower-body compression augments blood pressure (BP) and tissue perfusion. EECP effects on autonomic cardiovascular modulation and cerebral autoregulation (CA) still need to be determined. We tested the influence of EECP on autonomic cardiovascular modulation and CA in healthy controls. Methods: In 23 healthy persons (27.9 ± 4.0 years), we monitored heart rate (HR), mean BP [Colin Pilot™] and middle cerebral artery blood flow velocity (CBFV) using transcranial Doppler sonography, before and during 5 min EECP. Respiration was paced at 12/min. During EECP, ECG-triggered pressure of 300 mmHg was rhythmically applied [Vasomedical,USA].We analysed spectral powers of the time series of HR, BP and CBFV in the low (LF: 0.04–0.15 Hz) and high (HF: 0.15–0.5 Hz) frequency ranges and calculated the LF transfer function gain and phase shift of BP and CBFV as indices of cerebral autoregulation. Results: During EECP, HR (72.7 ± 9.0 vs. 75.6 ± 8.6 bpm) and BP (83.4 ± 10.2 vs. 86.2 ± 9.8 mmHg) increased while CBFV (55.0 ± 18.5 vs. 50.1 ± 17.0 cm/s) and LF-power of BP (2.4 ± 1.4 vs. 1.1 ± 0.6 mmHg2) decreased. LF-power of CBFV (2.0 ± 1.2 vs. 2.6 ± 2.1 (cm/s)2), normalized LF-power (33.9 ± 19.9 vs. 35.9 ± 16 %) and HF-power of HR (66.1 ± 19.9 vs. 64.1 ± 16 %) remained stable. EECP did not change the transfer function gain (0.8 ± 0.3 vs. 1 ± 0.5 cm/s/mmHg) and phase shift (0.8 ± 0.3 vs. 0.9 ± 0.4 rad). Conclusion: Stable LF- and HF-powers of HR, LF-power of CBFV as well as gain and phase shift during EECP indicate that EECP does not compromise cerebral autoregulation and has no major effect on autonomic cardiovascular modulation in healthy persons.

Obesity and its influence on cardiovascular hemodynamics Albert Holler, Harald Mayer, Jörg Lindenmann, Falko Skrabal Krankenhaus Barmherzige Brüder, Teaching Hospital Karl Franzens University, Marschallgasse 12, A-8020 Graz, Austria Purpose of the study: To clarify the effect of obesity on baroreceptor reflex sensitivity and total peripheral resistance. Methods: A sample of consecutive patients with BMI greater than 25 who underwent tilt-table-testing, were evaluated for abnormal hemodynamic reactions. 53 subjects who were all normotensive were included in the study. The patients were stratified into two groups: a) moderately obese with a BMI 25 to 30 and b) a group of morbidly obese subjects with BMI > 30. From the above groups 18 pairs were matched for age and gender. Results: During the phase of 60° head up tilt the Index of total peripheral resistance (TPRI) showed a marked fall in the group with BMI > 30 as compared to the moderately obese patients. The mean values of the differences of TPRI were 11,96 % (95 % CI 10,01–19,97), p < 0,001. The baroreptor effectiveness index (BEI) of the spontaneously occurring up-and-down events of the baroreceptor reflex episodes during the initial supine position also showed a significant difference with higher BEI in the BMI-group > 30: mean difference of the event rate 13,94 (95 % CI 3,35–20,65), p < 0,01. Conclusion: The rapid fall of TPRI in the subjects with morbid obesity may be due to a limited reaction of the central adrenergic system during the tilting manoeuvre because of its higher basal level of

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activity which is characteristic of obesity. Another reason could be a lower peripheral resistance of the blood vessels of adipose tissue as compared to lean tissue. Although it is known that obesity is associated with lower baroreflex sensitivity, the increased occurrence of baroreceptor reflex events (BEI) in the morbidly obese group could possibly be explained by a higher venous return of blood to the heart, resulting in higher filling pressure, thus stimulating the cardiopulmonary baroreceptors.This effect could be produced by the large burden of the intraabdominal fat mass weighing on the large vessels and the diaphragm. These results indicate also a higher haemodynamic instability in morbidly obese subjects which is related to the mass of adipose tissue.

Dynamics of oxygen delivery during moderate exercise in humans Lador F, Azabji-Kenfack M, Moia C, Morel D*, Ferretti G Department of Physiology, University Medical Centre; *Division of Anesthesiology, Geneva University Hospital, Geneva, Switzerland Purpose of the Study: The kinetics of O2 consumption (VO2) at the onset of exercise require a precise matching to that of O2 delivery (QaO2). Thus, the kinetics of QaO2 should be faster than that of VO2.To our knowledge, the kinetics of QaO2 were never determined on humans so far. The aim of this study was to determine on humans QaO2 on a beat-by-beat (BB) basis during moderate square wave exercise. An analysis of QaO2 at steady-state is also proposed. Methods: QaO2 was determined on 7 men (age 24.0 ± 2.9 yrs, VO2max 4.32 ± 0.61 L.min-1), who performed 4 rest-to-50W and rest-to-100W transitions on a cycle ergometer. BB Q was measured by the model flow method from continuously recorded pulse pressure profiles. Arterial oxygen saturation (SaO2) was measured by infrared oximetry. Blood haemoglobin concentration ([Hb]) was measured every min. The time courses of [Hb] and SaO2 were computed by interpolating the data by means of a 6th degree polynomial. BB QaO2 was calculated as: Q*SaO2* [Hb]*1.34 (O2 binding coefficient to [Hb]). Results: The time constants of the QaO2 kinetics were 7.18 ± 3.53s in the rest-to-50 W and 10.97 ± 3.97s in the rest-to-100 W transitions. Steady state QaO2 was proportional to power, and showed oscillations around its mean value (3.08 + 0.38 L.min-1 and 3.88 + 0.28 L.min-1 at 50 and 100 W, respectively), with a frequency of 0.077 + 0.010 Hz at 50W and 0.082 + 0.016 Hz at 100 W. The oscillation amplitude was 0.148 + 0.067 L.min-1 at 50 W and 0.173 + 0.051 L.min-1 at 100 W. Conclusion: The QaO2 kinetics are faster than those reported for O2 uptake, in agreement with the tested hypothesis.They reflect the rapid Q response by the Frank-Starling mechanism, and suggest O2store changes at exercise onset. The Q- and QaO2-oscillations at steady state may be due to arterial baroreflexes.

The Haemodynamic and Autonomic Consequences of Alpha-Blockade during Passive Head Up Tilt as compared to Age Matched Untreated Controls and Patients on ACE-Inhibitors Jörg Lindenmann, Harald Mayer, Gerfried Gratze, Falko Skrabal Department of Internal Medicine, Krankenhaus der Barmherzigen Brüder, Teaching Hospital of the Karl Franzens University, Marschallgasse, Graz, Austria Purpose of the study: The ALLHAT study reported an increased mortality from heart failure in patients on alphablockers as compared to HCT, ACEI and Ca-antagonists. The reason for this increased mortality is not clear. Therefore we evaluated the haemodynamic response

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to orthostasis in healthy subjects, in age matched patients on alphablockers and in age matched patients on ACEI. Methods: The haemodynamic response to passive head up tilt was evaluated using the Task Force Monitor™ (CNSystems, Austria), which provides non invasively on a beat to beat basis: heart rate (HR), stroke index (stroke volume/m2 BSA), cardiac index (cardiac output/m2 BSA), systolic BP, diastolic BP, total peripheral resistance (TPRI), sympathetic-vagal balance by spectral analysis of heart rate variability and blood pressure variability (LF/HF ratio) and baroreceptor reflex sensitivity (BRRS) by the sequence method. We compared 23 healthy subjects (f = 8, m = 15, age range 46 to 83, mean age 65.1) with 23 patients on alphablockers (f = 1, m = 22, age range from 47 to 84, mean age 68.5) and 23 patients on ACEI (f = 16, m = 7, age range from 58 to 82, mean age 72.3). The subjects were investigated during supine bed rest (10 minutes) and after passive head-up tilt to 60° for 15 min. Results: In patients on alpha blockade as compared to untreated healthy subjects and to patients on ACEI a significantly enhanced increase of HR after head up tilt (∆ HR 9.9 ± 6.76 vs 7.6 ± 4.66 vs + 5.8 ± 5.46 ‘mean ± SEM, p < 0.025 for the difference) was observed. Patients on alphablockers as compared to controls also showed a significantly blunted decrease of stroke index after head up tilt (∆ SI –12.4 ± 7.14 vs –4.6 ± 7.28,p < 0.0005).Whereas in untreated subjects TPRI rose after head up tilt by 10.6 mmHg*min*m2/l, p < 0.010 and in patients on ACEI by 6.5 ± 14.49 mmHg*min*m2/l, it fell during alpha-blockade by 2.1 ± 11 mmHg*min*m2/l. There were no significant differences in BRRS, or modulation of BRRS by tilt between the three groups. Whereas ACE inhibitors caused a decrease in sympathicovagal balance (LF/HF ratio) during head up tilt (∆ –1.0 ± 6.43), untreated subjects showed a rise of the LF/HF ratio (∆ + 2.4 ± 3.04, p < 0.04 for the difference) which was even more pronounced in patients on alpha blockers (∆ + 5.9 ± 15.89). Conclusions: During orthostasis patients on alpha-blocking drugs must compensate a paradoxical significant fall of TPRI by a significantly higher drive to the heart, not only indicated by the increase of the LF/HF ratio but also by a signifantly enhanced rise of HR and by less decrease in stroke volume after head up tilt. The observed haemodynamic alterations in patients on alpha blockers would implicate a higher sympathetic drive of and a higher mechanical burden to the heart during the many hours of upright position during day time. These changes may be sufficient to explain the higher incidence of heart failure observed in patients with coronary heart disease treated with that particular class of antihypertensives. Supported by the FWF Austria, SFB007.

Haemodynamic reactions in youths with high blood pressure level – the author’s own observations Lidia Ostrowska – Nawarycz, T. Nawarycz Department of Human Physiology and Biophysics, Medical University, Lodz, Poland Purpose of the Study: The aim of this paper was to evaluate parameters of the cardiovascular system in youths with high blood pressure. Methods: 30 boys with high blood pressure level, between 14–19 years of age, and 29 normotensive boys of similar age were examined. The changes of haemodynamic parameters were evaluated during functional cold pressor and Valsalva manoeuvre tests. Results: Parameters of the cardiovascular system in youths with high blood pressure in the resting condition were higher than in normotensive youths. Upon cold pressor testing of boys, we observed three types of blood pressure reactions: hyperreactions, normoreactions and hyporeactions. The heart rate (HR), mean blood pressure (MBP) as well as the cardiac index (CI),left ventricular work index (LVWI) and the Heather index (HI) showed statistically significant changes. Similar

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changes of the above parameters were observed during the Valsalva manoeuvre. Conclusion: Haemodynamic parameters of hypertensive boys changed into the same direction as in their normotensive controls, albeit in an exaggerated fashion. These changes might be indicative of a more intense reacticity of their autonomic system.

Ambulatory pulse pressure is a relatively sleep-independent variable Gila Perk, Michael Bursztyn Hadassah University Hospital, Mount-Scopus, Jerusalem, Israel Purpose of the Study: Blood pressure has been described as consisting of a pulsatile component (pulse pressure) and a steady component (mean arterial pressure). The former is related to ventricular contraction, arterial stiffness and wave reflection, while the latter is determined by peripheral vascular resistance and cardiac output. Several studies have shown that pulse pressure is a potent predictor of cardiovascular risk. Many factors are known to influence blood pressure, e. g. sympathetic activity, diet and state of alertness. However, the effect of sleep on pulse pressure has not been addressed before. We undertook this study in order to clarify this effect. Methods: We studied 240 consecutive subjects who were referred to our unit for ambulatory blood pressure monitoring. There were 99 males and 141 females, the majority of which were treated hypertensives. Mean age was 58.5±17.0 years. Thirty three subjects were diabetic, 75 non-dippers. Results: Twentyfour hour mean arterial pressure (MAP) was 97.1±9.8 mmHg. Awake and asleep MAP were 100.6±9.9 mmHg and 87.6±10.3 mmHg respectivly. Twentyfour hour, awake and asleep pulse pressure were 59.6 + 12.6 mmHg, 60.1±12.7 mmHg and 57.8±13.1 mmHg. MAP dip was 12.8 %, 95 % confidence interval (CI) 11.9–13.7 whereas pulse pressure dip was 3.7 %, 95 % CI 2.6–4.8. Thus, MAP dip was more than 3.5 times the pulse pressure dip (p < 0.0001). This held true for diabetic, male, female, obese, elderly or young subjects.Pulse pressure correlated strongly with systolic blood pressure (correlation coefficient 0.70, p < 0.0001). However, despite the high correlation between the two parameters, systolic blood pressure dip was more than 2.5 times the pulse pressure dip (p < 0.0001). Conclusion: Thus, the more rigid nature of pulse pressure may make it a variable with a better predictive power.

Effects of sodium profile dialysis and cooled dialysate on haemodynamics and autonomic regulation Martin Tiefenthaler, Gudrun Radacher, Gert Mayer Department of Nephrology, University of Innsbruck, Austria Purpose of the Study: Blood pressure instability is a major complication of patients with end stage renal disease on haemodialysis. To date sodium profile dialysis and dialysis with cooled dialysate are generally applied strategies to treat patients suffering from frequent hypotonic episodes during dialysis. To date the effects of these manoeuvres on haemodynamics and autonomous regulation have not been studied. Methods: Fifteen patients were randomly subjected to dialysate sodium profile (150 falling to 138 mmol/l) vs. constant dialysate sodium patients (138 mmol/l) and to dialysate temperature of 35 vs. 37 °C. Ultrafiltration was similar in each pair of examinations. With the TFM-1 monitor haemodynamics and autonomic regulation were recorded for 2h. Results: Preliminary data of 11 completed patients indicate that total peripheral resistance index (TPRI) is increased in dialysis with

sodium profile when compared to control. However, dialysate temperature at 35 °C does not result in increased TPRI in the subjects studied.In a previous study with an ultrasound dilution method it has been shown that cool dialysate as well as normal dialysate temperature caused an increase in TPRI. Conclusion: The results of the different dialysis regimens on autonomic regulation will be analysed after completion of the study and presented at the meeting.

Effects of continuous mask positive airway pressure ventilation (CPAP) on cardiopulmonary haemodynamics and baroreflex sensitivity A Valipour1, 2, H. Pils3, I Schmidt1, W Kössler1, 2, OC Burghuber1, 2 1 Department of Respiratory and Critical Care Medicine, Otto-Wagner-Hospital; 2 Ludwig-Boltzmann-Institute for COPD Research; 3 FA für Innere Medizin, 1010 Vienna Purpose of the Study: Continuous positive airway pressure (CPAP) ventilation is frequently used for the treatment of patients with sleep apnoea, in acute pulmonary oedema and during weaning procedures from invasive mechanical ventilation. Elevations in intrathoracic pressure generated by CPAP may induce haemodynamic alterations and affect baroreflex sensitivity (BRS). Methods: To test this hypothesis we studied eight healthy volunteers (5 men/3 women) during short term exposure to three different ventilatory settings in a random order: normal breathing (NB), CPAP delivered via nose mask with the pressure set at 5 cm H20 (CPAP low) and 15–20 cm of H20 (CPAP max). Heart rate (HR), cardiac output (CO), stroke volume (SV), continuous mean blood pressure (BPm), total peripheral resistance index (TPRI), heart rate variability (HRV) and BRS were recorded simultaneously (Task Force Monitor 3040, CNSystems, Graz). Results: There was no difference in any of the variables between NB and CPAP low. However, CPAP max produced a significant, reversible, decrease in cardiac output (p < 0.01) and stroke volume (p < 0.01), while TPRI increased (p < 0.005). BPm and HR remained unchanged. Furthermore, we observed a reduction in the total power of HRV (p < 0.05) during CPAP max, with an increase in the very low frequency components (p = 0.05) of HRV. Finally, there was a decrease in BRS (p < 0.05) in our subjects while on maximal pressures of CPAP ventilation. Conclusion: High pressures of mask CPAP ventilation result in significant haemodynamic alterations and exert a reversible stress response in healthy subjects.

Instantaneous Changes In Middle Cerebral Artery Blood Flow Velocities During Manual Common Femoral Artery Compression Reinhard Volkmann, Peter Friberg, Sinsia Gao, Walter Osika Department of Clinical Physiology, Cardiovascular Institution, Sahlgrenska University Hospital, Göteborg Sweden Purpose of the Study: Blood flow distribution to parallel coupled organs is inversely related to the impedance in each of the branching circuits. The systolic blood flow distribution is not limited under physiological conditions, i. e. the great branching circuits and the windkessel are adequately supported by the cardiac stroke volume by means of relatively high blood pressure driving forces. However, the diastolic blood volume flow is driven by reduced pressure gradients and limited by the maximum windkessel volume output. Therefore, different organ systems compete for the limited diastolic windkessel volume by means of local impedance modulation. Only central autonomic control overcomes tendencies of chaotic flow distributions.

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Nonlinear analysis of complex phenomena in cardiological data

Methods: Pulse waveforms were recorded using the non-invasive technique of photoplethysmography (PPG) from the right and left ear lobes, index fingers and great toes of 116 healthy human subjects. Their median age was 41 years (range 13–72 years) allowing four distinct age groups to be considered (subjects younger than 30 years, from 30 to 39 years, from 40 to 49 years, and those 50 years of age or older). The PPG pulses from the ear, finger, and toe sites were normalized in both width and height and their shapes averaged over 60 consecutive good quality heart beats. Normalized shapes were then calculated for the whole subject group, and for the subjects within each of the four age groups. The differences in shape, relative to the oldest subject group, were also calculated for two regions of interest of the pulse: for the systolic rising edge, and the dicrotic notch. Results: Subtle but significant changes in the normalized PPG pulse shape were found at all sites with overall elongation of the systolic rising edge (p < 0.05) and damping of the dicrotic notch (p < 0.05) with advancing age. Conclusion: The subtle age-related changes in multi-site PPG pulse shape characteristics at the ear, finger and toe sites have been demonstrated and quantified. Age-matched normal ranges are recommended when evaluating PPG pulses from patients with possible peripheral vascular disease.

Niels Wessel1, Hagen Malberg2, Alexander Schirdewan3, Jürgen Kurths1 1 University of Potsdam; 2 Karlsruhe Research Center; 3 Franz-Volhard-Hospital Berlin, Germany

Time- and frequency-analysis of the Korotkoff Sounds

Methods: To test influence of rapid impedance changes on blood flow distribution between two organ systems, middle cerebral artery (MCA) blood flow velocity was measured continuously in five healthy volunteers before, during and after bilateral manual compression of the common femoral arteries(CFA). The CFA clamping time was two minutes. Directly after CFA compression release, flow velocities were also measured on one side of the CFA. Results: The first MCA blood flow profile at CFA compression showed increasing velocities during the whole cardiac circle, which was followed by autoregulation to base line within three to five heart beats. The opposite changes occurred during CFA clamp release. Immediately after clamp release, orthograde diastolic CFA flow velocities were observed, which decreased and changed direction within few beats. Conclusion: Our findings support the hypothesis of competition for a limited blood flow input between parallel coupled circulatory units, but differences between systole and diastole could not be shown.

Purpose of the Study: The main intention of this contribution is to discuss different nonlinear approaches to heart rate- and blood pressure-variability analysis for a better understanding of the cardiovascular regulation. Methods: We investigated measures of complexity which are based on symbolic dynamics, renormalized entropy and the finite time growth rates. The dual sequence method to estimate the baroreflex sensitivity and the maximal correlation method to estimate the nonlinear coupling between time series are employed for analysing bivariate data. The latter appears to be a suitable method to estimate the strength of the nonlinear coupling and the coupling direction. Heart rate and blood pressure data from clinical pilot studies and from very large clinical studies are analysed. Results: We demonstrate that parameters from nonlinear dynamics are useful for risk stratification after myocardial infarction, for the prediction of life-threatening cardiac events even in short time series, and for modelling the relationship between heart rate- and blood pressure- regulation. Conclusion: These findings could be of importance for clinical diagnostics, in algorithms for risk stratification, and for therapeutic and preventive tools of next-generation implantable cardioverter-defibrillators.

The arterial wall Age-related changes in photoplethysmographic pulse shapes at various body sites J Allen, Principal Clinical Scientist Professor A Murray, Professor of Cardiovascular Physics Cardiovascular Physics and Engineering Research, Regional Medical Physics Department, Freeman Hospital, Newcastle upon Tyne. UK. Purpose of the Study: Peripheral pulse characteristics can be affected by age and by vascular disease. It is important therefore to quantify and understand age-related changes at different body sites in normal subjects before studying patient data. The aim of this study was to determine the association between age and changes in pulse shape characteristics at the ears, fingers, and toes.

Dr J Allen, Mr T Gehrke, Dr J O’Sullivan, Professor A Murray Departments of Medical Physics and Paediatric Cardiology, Freeman Hospital, Newcastle upon Tyne, UK. University of Applied Sciences, Gelsenkirchen, Germany. Purpose of the Study: The sounds associated with the five classical Korotkoff phases are clinically important for measuring systolic and diastolic blood pressures. The frequency ranges of the sounds have been described using the overall peak frequencies within each phase by simple Fourier methods. However, such analysis may be missing potentially useful clinical information [1]. The aim of this study was to use a time-frequency-analysis (TFA) technique to extract features associated with the Korotkoff sounds obtained during blood pressure measurement and to compare these with the phases allocated by an expert cardiologist. Methods: A single operator recorded Korotkoff sounds from 6 healthy subjects using a measurement system comprising: cardiology stethoscope, microphone, amplifier, a recording system for computer sound digitization and a MiniDisc system for playback to the cardiologist for phase classification [1]. Results: TFA demonstrated three main types of frequency components: low frequency (< 80 Hz), high frequency (100–250 Hz) spike and murmurs, which, when present, followed the spike for up to 150 ms. Qualitatively, the phase changes within subjects showed that phase 2 was most complex, having the greatest degree of murmur and phase 4 having the lowest frequency range. Conclusion: The TFA approach to Korotkoff phase analysis was able to identify characteristic differences associated with the different phases classified by the expert cardiologist. Reference 1. O’Sullivan J, Allen J, Murray A (2002) The forgotten Korotkoff phases: how often are phases II and III present and how do they relate to the other Korotkoff phases? Am J Hypertens 15:264–268

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Arterial Dynamics: Relationship between Sphygmocardiography and CR-2000 Cardiovascular Profile in Mild Essential Hypertension Adel Birbari, Asma Lakiss, Samir Arnaout, Samir Mallat American University of Beirut Medical Center, Department of Medicine, Beirut Lebanon Purpose of the Study: Epidemiologic data indicate that arterial stiffness is a strong predictor for cardiovascular morbidity and mortality. In the present study involving 182 patients with mild essential hypertension, arterial compliance a surrogate measure of arterial stiffness was evaluated by both Sphygmocardiography and CR-2000 Cardiovascular Profile techniques. To correlate arterial dynamics with degree of target organ damage, creatinine clearance (Ccr) and echocardiography were also determined in all patients, as well as a fasting blood glucose (FBG). Patients were divided into 4 age groups (GI < = 40; GII 41–50; GIII 51–60; GIV 61 +). Results: Data were as follows (GI to GIV): Age yrs (31 ± 7, 46 ± 0.3, 55 ± 0.2, 67 ± 0.3); SBP mmHg (136.6 ± 7, 139.3 ± 1.8, 149.9 ± 1.9, 154.1 ± 2.4); DBP mmHg (88 ± 1.2, 92 ± 1.2, 91.5 ± 1.1, 84.5 ± 1.0); MAP mmHg (104.4 ± 1.2, 107.9 ± 1.4, 110.8 ± 1.2, 107.8 ± 1.2); PP mmHg (48.6 ± 1.4, 47.2 ± 1.3, 58.1 ± 1.6, 69.5 ± 2.2), FBG mg/dl (96.5 ± 1.5, 103 ± 2.1, 109 ± 2.2, 114 ± 2.8); Ccr ml/min (98.4 ± 2.6, 88.4 ± 2.9, 84.4 ± 2.5, 69.3 ± 3.1); LVmass g/m 2.7 (57.7 ± 2.6, 56.6 ± 2.1, 64.2 ± 3.3, 73.2 ± 3.2); augmentation index % (11.0 ± 2.3, 22.6 ± 1.9, 26.3 ± 1.5, 29.2 ± 1.5); Capacitive compliance (C1) ml/mmHgx10 (15.8 ± 0.7, 15.9 ± 0.8, 13.4 ± 0.4, 11.3 ± 0.5); Reflective compliance (C2) ml/mmHgx100 (7.2 ± 0.4, 5.7 ± 0.4, 4.6 ± 0.4, 2.9 ± 0.20). Conclusion: In mild untreated essential hypertension (1) alterations in arterial dynamics first appear after the age of 40 years; (2) decreased distal arterial compliance C2 reported to be a measure of endothelial dysfunction is the initial change causing an increase in arterial stiffness; (3) with ageing arterial vascular changes become more generalized, more severe and are associated with an increase in SBP and PP and target organ damage (LVH and reduced Ccr); (4) glucose intolerance probably contributes to the age-related arterial changes.

The association of endothelial dysfunction with endothelial nitric oxide synthase gene polymorphism in essential hypertension and heart failure: A controlled study Demirel S¸*, Gençhellaç H**, Çine N***, Oflaz H****, Ala M*, Vatansever S*, Akkaya V*, Erk O*, Dilmener M* * Istanbul University, Department of Internal Medicine; ** Department of Radiology; *** Department of Genetics; **** Department of Cardiology Purpose of the Study: Endothelial dysfunction is now recognized as an early initiating event in the cardiovascular disease continuum. Endothelial constitutive nitric oxide synthase gene polymorphism (ecNOS) has been shown to be associated with many cardiac risk factors. Our purpose was to evaluate for the first time the influence of the ecNOS on endothelial function in essential hypertension (EH) and heart failure (HF). Methods: 116 healthy young controls (M/F 48/68, 33.6 ± 9.1 years), 104 HF (M/F 71/33, 63.1 ± 10.1 years), 101 EH (M/F 41/60, 44.9 ± 6.9 years) patients were included. The variable number of tandem repeats of ecNOS gene were amplified by polymerase chain reaction to determine the number of repeats. The brachial artery was imaged using a 7.5MHz linear phased-array ultrasound transducer.Endothelium dependent (EDD) and independent (EID)vasodilation was assessed.All the patients were under therapy since nearly 5 years. Results: 2 alleles (a, b) containing 4 and 5 repeats were idendified. The bb and aa + ab genotypes in controls EH and HF were 98/18,

76/25 and 83/21, respectively. There was no statistically significant difference between controls and patient groups for genotype frequencies (p = 0.09). Controls (n = 81) and EH (n = 30) patients showed similar responses to EDD and EID. However, HF (n = 18 because of 12 hypotensive episodes with nitrates) patients had significantly lower EDD(12.0 ± 9.2 % vs 22.5 ± 7.2 %, p < 0.001) and EID (15.7 ± 7.6 % vs 26.3 ± 8 %, p < 0.001) values compared to controls. Ab genotype patients with HF had lower EDD(3.1 ± 1.4 % vs 14.5 ± 8.9 %, p = 0.023) and EID (8.0 ± 3.3 % vs 17.9 ± 7.1 %, p = 0.016) values compared to bb genotype. Conclusion: It was concluded, that the influence of ecNOS aa + ab genotype was only expressed under the pressure of selective disease states like HF despite optimal medical therapy.

In vitro inhibitory effects of barley grass extracts on vasoconstriction induced by several agonists U. Eder, M. Butter, R.Wintersteiger, F.Bucar, H. Juan Institut für Biomedizinische Forschung Purpose of the Study: The young leaves of barley (Hordeum vulgare L., Gramineae), called barley grass, are rich in nutrients and promoted as food supplement.They are claimed to have antioxidant and anti-inflammatory activity, but with the exception of the antioxidant effect there is very limited scientific evidence to substantiate these claims. Results of our previous study with isolated coronary arteries labelled with 14C-arachidonic acid, showed a 4-fold increase of prostacyclin formation after stimulation with Ca++-ionophore A23187. In addition, the phospholipid- and PGE2-release (40,1 % and 49,0 %, resp.) was inhibited significantly (p < 0,05). Methods: Assuming a possible vasodilating effect, we investigated the influence of aqueous barley grass extract on vasoconstriction by experiments with isolated bovine coronary artery strips. Pre-incubation of the vessels with the extract inhibited the constrictions to histamine, serotonine, the thromboxane mimetic U46619 and the isoprostane 8-epi prostaglandin F2 in a concentration-dependent manner (1 to 9 mg/ml). Results: The results suggest a non-specific inhibition of these vasoconstrictor effects. L-NAME caused a decrease of the vasodilating response, which supports the impression, that the effect is in part NO-mediated. Furthermore it was demonstrated, that prostacyclin is not involved in the in vitro-relaxation (no effect of indomethacin). To characterize the vasoactive principle, bioassay-guided fractionation-steps are in progress. Preliminary phytochemical investigations give evidence of a very hydrophilic compound with a molecular weight below 1000 Da. Conclusion: We conclude that our findings, combined with the known effects of antioxidant compounds in barley grass, may become relevant in treating cardiovascular diseases.

Blood pressure and arterial wall properties in the families of hypertensive patients and of control subjects J. Filipovsky, M. Ticha, P. Roucka 2nd Department of Internal Medicine, University Hospital, Pilsen, Czech Republic Purpose of the Study: To evaluate blood pressure (BP), properties of large arteries and the extent of the pressure wave reflection in hypertensive and control families. Methods: We examined 40 families (at least one parent and two children, all 18–59 years of age): 23 families were derived from a treated hypertensive patient and 17 from a healthy subject; altogether, 133 subjects were examined. Pulse wave analysis (PWA) on radial

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artery and pulse wave velocity (PWV) on aorta and lower limb were performed using the Sphygmocor device; by means of PWA, the magnitude of reflected pressure wave was estimated, while the arterial wall rigidity was re-flected by the PWV. Results: The reflected pressure wave was significantly higher in treated hypertensive patients than in healthy adults (p < 0.0001).It increased significantly with age and was higher in parents than in their offsprings (p < 0.0001 in the families of both hypertensive patients and of controls). Systolic and diastolic BP were significantly higher in the offsprings of hypertensive patients than in children of healthy subjects (mean systolic BP 124 vs 108 mmHg, p < 0.0001). Aortic PWV was higher in treated hypertensives than in control adults (7.4 vs 6.2 m/s, p < 0.005); the difference between offsprings was not significant. No difference of PWV in lower limbs was found among the groups. Conclusion: 1. Middle-aged treated hypertensive subjects have higher aortic rigidity and a higher reflected pressure wave despite a good BP control (mean BP 128/85 mmHg). 2. Offsprings of hypertensives have significantly higher BP than offsprings of controls but they do not differ in their pressure wave reflection or in their rigidity of aorta and lower limb arteries. Supported by the grants No.CEZ J13/98:11400001 and.NG 6757–4.

Lack of association of the V249I polymorphism of CX3CR1 with endothelial dysfunction and coronary artery disease Alexander Gugl1, Isabella Schmoelzer, Wilfried Renner, Gerald Seinost, Ernst Pilger1, Bernhard Paulweber, Bernhard Iglseder, Peter Schmid, Thomas C. Wascher2 1 Division of Angiology, Department of Medicine, University Hospital, Graz, Austria; 2 Department of Medicine, University Hospital, Graz, Austria Purpose of the Study: Recently, a polymorphism (V249I) in the fractalkine receptor CX3CR1 has been associated with a lower risk of coronary artery disease and better endothelial function. The lack of a healthy, asymptomatic control group in that study prompted us to carry out measurements of endothelial function by brachial artery ultrasound in healthy individuals grouped by genotype, and furthermore to test the involvement of the V249I polymorphism in coronary artery disease in a matched case control study. Methods: In a nested case control study 9 VV and 9 VI subjects were matched by genotype, age and gender. Brachial artery ultrasound scans were taken to test endothelium-dependent (flow-mediated,FMD) and endothelium-independent (nitroglycerin-mediated,NMD) dilation. In addition, 404 coronary artery disease patients and age- and sex-matched controls were genotyped by polymerase chain reaction and restriction-fragment-length-polymorphism methods. Results: Among healthy subjects, neither endothelium dependent (FMD: VV: 7.6 ± 3.2 % versus VI: 7.6 ± 2.5 %, P = 0.69), nor endothelium independent (NMD: VV: 15.8 ± 4.1 %; VI: 15.6 ± 5.4 %; P = 0.72) dilation differed. Also for genotype distribution among coronary artery disease patients, no significant difference could be detected.When tested as two class variables (VV versus VI/II), the adjusted odds-ratio of the I-allele associated with CAD was 0.99 (95 % CI: 0.65–1.54; P = 0.99). Conclusion: We were unable to show an association between the V249I polymorphism and brachial artery endothelial function or coronary artery disease.

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Women and Men: the Augmentation Index and Inflammation Kampus P1, Kals J2, Ristimäe T1, Pulges A3, Zilmer M2, Teesalu R1 1 Department of Cardiology; 2 Institute of Biochemistry; 3 Department of Cardiovascular and Thoracic Surgery; University of Tartu Purpose of the Study: Inflammatory processes play a principal role in the pathogenesis of atherosclerosis. Atherosclerotic arteries become stiff at an early stage of the disease. Decreased distensibility of large arteries and inflammation are important determinants of cardiovascular risk. The aim of this study was to investigate the association between the augmentation index (AIx) and circulating markers of inflammation in healthy women and men. Methods: Pulse wave analyses were performed and plasma samples were collected in 133 healthy Estonian residents (52 males and 81 females) age 40–59. Pressure waveforms were recorded from the radial artery and corresponding central waveforms were generated using SphygmoCor 8,1 software.Then the AIx was determined as a measure of systemic arterial stiffness. Results: The AIx was significantly higher in females when compared to males (24,7±8,4 % vs 11,4±12 %, p < 0,0001). The AIx was also significantly higher in patients with high-sensitivity C-reactive protein (hs-CRP) levels above 1 mg/L (in women 27,4±7,7 % vs 22,2±8,4 %, p = 0,005; in men 16,1±5,9 % vs 8,5±13 %, p = 0,03) and white blood cells (WBC) count above 6000/µL (in women 31,2±8,5 % vs 23,4±7,9 %, p = 0,002; in men 18,2±7,6 % vs 8,1±12,4 %, p = 0,003). Conclusion: Asymptomatic subjects with higher values of circulating markers of inflammation (WBC count and hs-CRP) presented with stiffer arteries. Possibly, the increased arterial-wall stiffness, together with elevated inflammatory markers in an unselected middleage population, may provide important information on early changes of atherosclerosis, especially in persons with concomitant risk factors for cardiovascular disease.

Intima media Thickness, Augmentation index and Baroreceptor Reflex Sensitivity as Predictors of Cardiovascular Risk: Their Interrelation and their Relation to Biochemical Cardiovascular Risk factors Harald Mayer, Jörg Lindenmann, Gerfried Gratze, Falko Skrabal Krankenhaus der Barmherzigen Brüder, Teaching Hospital of the Karl-Franzens-University, Graz, Marschallgasse, Austria Purpose of the Study: Intima Media Thickness (IMT), Augmentation Index (AI) and Baroreceptor Reflex Sensitivity (BRRS) have all been established as predictors of cardiovascular death independent of the established biochemical risk factors. To our knowledge the interrelation of IMT, AI and BRRS has not been studied, although all three could reflect a comparable physical marker for the same disease process of large arteries. Methods: The IMT (Powervision 6000™, Toshiba with a 7.5 mHz transducer), AI (Sphygmocor™, AtCor Medical, Australia), and BRRS (Task Force Monitor™, CNSystems, Austria) were measured in 50 patients (f = 26, m = 24, age range 21 to 88) with and without established atherosclerosis. In addition the following parameters were also included in the analysis: age, BMI, smoking status in pack years (py), total serum cholesterol, LDL-, HDL-cholesterol, triglycerides, homocystin, fasting BG, and HbA1c. Statistical analysis was performed using SPSS (single and partial correlation and multiple regression analysis). Results: IMT was related significantly to AI (r = 0.63, p < 0.0001, n = 50), but when controlled for age, BMI and biochemical risk factors their relation disappeared (r = 0,14, p < 0.35) There was no rela-

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tion to BRRS (r = 0,05, p < 0,73) in the single or partial correlation analysis. IMT was predicted only by the age of the patient (r = 0.75, p < 0.0001), but not by any other risk factors in the single or partial correlation analysis. The AI was significantly related to age (p < 0.0001), and total cholesterol (p < 0.005), combined R = 0.81, p < 0.0001, but not to LDL, HDL or their ratio. (LDL/HDL r = 0,27, p < 0,068, n. s.). The AI was not related to BRRS in the single or partial correlation analysis (r = 0,06, p < 0,72). The BRRS was only related to HDL (r = 0,39, p < 0.012) in the partial correlation analysis controlled for age and BMI. Conclusions: The principle predictor of AI is age and cholesterol but not the LDL/HDL ratio. The principle predictor of IMT is the age of the patient, the principle predictor of BRRS is the HDL of the patient. The relation between these three independently derived anatomic and functional characteristics of large arteries, namely AI, IMT and BRRS disappears if age,BMI and biochemical risk factors are taken into account. Since each of the three parameters is per se a good predictor of cardiovascular mortality it is proposed that each of the above reflects a different and independent functional or anatomic characteristic of the state of large arteries. Therefore at present none of the three methods should be replaced by each other but they should be used combined to provide the most complete morphological and functional picture of the arterial wall. It is interesting to note that total cholesterol was in all different analyses constantly a better predictor of the arterial state when compared with LDL or HDL or their ratio, which could suggest that the present emphasis of the LDL/HDL ratio may overlook some important influence of total cholesterol. Supported by SFB007 of the FWF, Austria

Systolic hypertension of youth is characterized by exaggerated pulse pressure amplification in some individuals McEniery CM*, Edwards RC†, Thomas N†, Tyrrell S†, Brown MJ*, Cockcroft JR†, Wilkinson IB*. * Clinical Pharmacology Unit, University of Cambridge, U. K.; †Department of Cardiology, University of Wales College of Medicine, Cardiff, U. K. Purpose of the Study: Systolic hypertension has been reported in young, otherwise healthy individuals (< 35 years), and has been termed pseudohypertension. We compared peripheral and central blood pressure (BP) and arterial stiffness in young individuals with systolic hypertension (SHT), subjects with essential hypertension (EHT) and normotensive controls (NT). Methods: We recruited 43 subjects with SHT (peripheral systolic BP (PSBP) = 140 mmHg and peripheral diastolic BP (PDBP) < 85 mmHg); 27 subjects with EHT (PSBP = 140 mmHg and/or PDBP = 90 mmHg), and 311 NT (PSBP < 130 mmHg and PDBP < 85 mmHg). After 15 min rest, BP was measured in the arm and central BP and augmentation index (AIx, a measure of arterial stiffness) were determined using pulse wave analysis. Pulse pressure (PP) amplification was defined as peripheral PP – central PP. Results: PP amplification was significantly higher in SHT (28 ± 6 mmHg) compared with NT and EHT (17 ± 5 and 17 ± 6 mmHg, respectively). AIx was significantly lower in SHT and NT (–1 ± 15 and 0 ± 17 %, respectively) compared with EHT (11 ± 14 %). We further divided the SHT cohort into those above or below the mean + 2SD PP amplification in NT subjects (i.e 27 mmHg). Those with the highest amplification (n = 29) had a significantly lower AIx compared with NT (–6 ± 11 %, P < 0.01 vs NT). However, in those subjects with the lowest amplification (n = 14), AIx was significantly higher than NT (10 ± 15 %, P < 0.05 vs NT), and not different from EHT (P = 0.8). There were no differences in heart rate between any of the groups.

Conclusion: Those individuals with the highest amplification appear to have less stiff arteries than controls, whilst the reverse is true in those with relatively normal amplification. This suggests that SHT of youth is a heterogenous condition and that not all subjects have pseudohypertension.

Comparison of Pulse Wave Velocity obtained using the Complior and Sphygmocor systems Sandrine Millasseau, Sundip Patel, Simon Redwood, Phil Chowienczyk Kings’ College London, UK Purpose of the Study: Aortic pulse wave velocity, a measure of aortic stiffness, predicts cardiovascular risk. The aim of this study was to compare measurements from the Complior (Artech, France) and the Sphygmocor (Atcor, Australia) systems. Methods: Carotid-femoral (PWVcf) and carotid-radial pulse wave velocity (PWVcr) were assessed in triplicate with each device in random order in 20 subjects. Systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) were measured with an oscillometric device (Omron 705CP) before each PWV measurement. Carotidfemoral and the carotid-radial path lengths were estimated from surface markings. The same lengths were used for the 2 devices. Results: HR and BP did not differ significantly between measurements obtained with the Complior and Sphygmocor (mean difference ± SE: 0.9 ± 0.8 bpm for HR, 2.7 ± 1.5 mmHg for SBP and 2.5 ± 1.3 mmHg for DBP). The reproducibility of the Complior was 4.3 and 5.1 % for PWVcf and PWVcr, respectively and 4.8 and 6.4 % for the Sphygmocor. PWV obtained from the Complior correlated with that obtained from the Sphygmocor. (R = 0.96 and 0.91 for PWVcf and PWVcr respectively, each P < 0.001). However, the slope and/or intercept of the regression lines differed significantly from the line of identity (PWVcf: slope = 0.75 ± 0.05, intercept = 1.73 ± 0.55. PWVcr: slope = 0.75 ± 0.09, intercept = 2.56 ± 0.87). The Bland-Altman statistic, 2SD of the difference between measurements, was 1.2 m/s for PWVcf and 1.5 m/s for PWVcr, with an error increasing at higher PWV values. Conclusion: There is a systematic difference between PWV measurements obtained from the Complior and the Sphygmocor. More importantly, there is considerable variation between measurements obtained from these devices. This could relate to the type of transducer and the algorithm used to calculate PWV.

Relationship between systemic arterial stiffness and microalbuminuria in patients with untreated essential hypertension. P. Muda1, P. Kampus1, T. Ristimäe1, M. Zilmer2, R. Teesalu1 1 Dept. of Cardiology, University of Tartu; 2 Institute of Biochemistry, University of Tartu Purpose of the Study: To investigate the interaction between the augmentation index (AIx), a measure of the systemic arterial stiffness, and microalbuminuria, which has been shown to to be associated with the degree of endothelial dysfunction in patients with hypertension. Methods: We examined 40 male patients, age 52.8 ± 7.0 yrs, with untreated essential hypertension (EH) stage I–II, mean duration of EH 13.3 ± 11.3 yrs.Pressure waveforms were recorded from the radial artery and corresponding central waveforms were generated using Sphygmocor Px software. Microalbuminuria (MA) was determined in 24h urine. Age, height, brachial systolic and diastolic blood pressure were recorded for each patient.As a measure of correlation between

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variables, nonparametric Spearman rank order coefficients were calculated. Results: In the study group, mean AIx was 20.6 ± 10.7 % and MA was 9.0 ± 6.1 µg/min. MA > 15 µg/min, was present in 5 patients. AIx was positively correlated with age (R = 0.32, p < 0.04) and MA (R = 0.40, p < 0.02). No correlation was found between brachial systolic or diastolic blood pressure or height and AIx. Conclusion: In patients with untreated essential hypertension,systemic arterial stiffness correlated with clinically irrelevant microalbuminuria.

In Vivo Non-Invasive Identification of Cell Composition of Carotid Intimal Lesions: Validation of an UltrasoundBased Approach M. Puato, E. Faggin, M. Rattazzi, M. Paterni1, C. Morizzo°, M. Kozàkovà°, C. Palombo°, and P. Pauletto on behalf of the Study Group of Arterial Plaque, SIIA Dep. of Clinical and Experimental Medicine, University of Padova; 1 CNR Institute of Clinical Physiology, Pisa; ° Dep. of Internal Medicine, University of Pisa Purpose of the Study: To investigate whether differences in cellular composition of the shoulder of carotid plaque, a cell-rich, debris-free area, can be revealed by computer-driven analysis of ultrasound Images. Methods: In 26 patients referred for carotid endarterectomy, the shoulder region of the plaque eligible for surgery was identified by ultrasound. Digital images were obtained and evaluated using an ad hoc developed computer-driven system (Medical Image Processing, MIP). The gray-level distribution of the region of interest (ROI), along with some statistical parameters exploring the spatial distribution of pixels such as entropy and second angular moment, were analyzed. In the specimen retrieved through surgery, the area corresponding to the ROI was selected.Cryosections were examined using monoclonal antibodies specific to smooth muscle cells (SMCs), macrophages (MC), and lymphocytes. Computerized image analysis was carried out to quantify each cellular component of the lesion. Results: Mean gray-levels correlated directly to SMC content (r = 0.576, p = 0.002), and inversely to that of MC (r = –0.555, p = 0.003). Lymphocytes did not show any correlation. The prevalence of SMC, expressed as the ratio SMC/(SMC + MC), was related positively with entropy (r = 0.517, p = 0.007) and negatively with second angular moment (r = –0.422, p = 0.032). The quartiles of graylevels were useful for stratifying significant differences in cellular composition. Conclusion: Some cellular features of the shoulder region of carotid plaque are associated with specific videodensitometric patterns. This approach would disclose an in vivo, non-invasive prediction and monitoring of cell composition of the shoulder region and could be extended to the study of the thickened intima.

Alterations of lipid peroxidation parameters in primary arterial hypertension under amlodipine therapy Radenkovic S, Radenkovic N, Cvetkovic T Institute of Nephrology and Hemodialysis, Nis, Yugoslavia Dept. of Computer Science, Faculty of Electronic Engineering, Nis, Yugoslavia Purpose of the Study: The process of lipid peroxidation, producing primarily peroxidation products of lipids within the cell membrane of endothelial and smooth-muscle blood vessel cells, represents one of the most important factors in the progression of primary arterial hypertension (HTA).

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Therefore, a modern approach to HTA treatment does not just entail blood pressure lowering, but also the prevention, or at least suppression, of disorders (of which an oxidative disbalance is one of the more important) at the level of cellular and subcellular structures. Bearing that in mind, we aimed at evaluating: 1. the degree of lipid peroxidation, as one of the oxidative disbalance factors, in pts with HTA 2. whether the treatment with amlodipine influences alterations of lipid peroxidation parameters. Methods: The investigation included 65 individuals of both sexes, 43 ± 7 years of age, out of which 20 were healthy controls, and 45 individuals with HTA, comprising the clinical group. The degree of lipid peroxidation was determined by measuring serum malonylaldehyde (MDA) as the end-product of lipid peroxidation. A spectrophotometric method was utilized.MDA was determined before and after 6months of amlodipine monotherapy. Results: Before amlodipine treatment, HTA patients had significantly increased MDA values (14.65 ± 2.81 nmol/l) as compared to controls (9 ± 1.42 nmol/l; p < 0.01). After 6 months of amlodipine treatment, MDA values were found to be markedly lower in the experimental group (11 ± 1.37; p < 0.05). Conclusion: In the patients with primary HTA, processes of lipid peroxidation appear to be overactive; their retardation after amlodipine therapy suggests that amlodipine, in addition to its antihypertensive action, also has antioxidative effects.

Dose-response study to assess the effect of palmoil-based Vitamin E (tocotrienol) on arterial compliance in healthy humans Rasool AHG, Rahman ARA, KH Yuen, Tee GB, Sadiq MA, Yusoff K University Sains Malaysia and University Kebangsaan Malaysia, Malaysia Purpose of the Study: Major observational and clinical trials on vitamin E and cardiovascular effects mainly addressed vitamin E in the form of tocopherol. For tocotrienols, another group of vitamin E (from rice bran and palmoil), the existing human data are scant.The aim of this study is to look at the effects of different doses of palmoilbased tocotrienols on arterial compliance in healthy humans. Methods: This randomized, parallel-design, placebo controlled and blinded-end-point study involved 36 healthy male volunteers divided into 4 groups of 9 subjects each. The 4 groups received either placebo, 80, 160 or 320 mg of mixed tocotrienols daily for 2 months. Arterial compliance was assessed using carotid-femoral pulse wave velocity (PWV) and the augmentation index (AI) obtained via Sphygmocor. Blood pressure, PWV, AI and plasma tocotrienol concentrations were taken before and each month after starting treatment. Absolute change in arterial compliance at 2 months compared to baseline values were calculated for each group and compared. Results: Baseline values (mean ± SEM) for age, BMI, PWV, augmentation index and plasma tocotrienol concentrations are 23.28 ± 0.25yrs, 22.77 ± 0.61, 7.65 ± 0.12m/s, –4.94 ± 1.62 % and 37.70ng/ml, respectively. Changes in PWV at the end of 2 months, compared to baseline for placebo, 80 mg, 160 mg and 320 mg doses were –0.15 ± 0.16m/s, 0.09 ± 0.21m/s, –0.17 ± 0.18m/s and –0.3 ± 0.16m/s, respectively.Changes in the percentage of the AI for those groups were –0.5 ± 2.30, 2,94 ± 2.42, –5.17 ± 1.63 and –0.6 ± 1.70, respectively. Mean tocotrienol concentrations for those groups were 35.45 ± 13.90, 267.76 ± 67.40, 575.31 ± 112.19 and 689.97 ± 206.96ng/ml, respectively. Conclusion: Tocotrienol at doses used (80,160 and 320 mg daily) did not have an effect on arterial compliance in healthy males.

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Mechanical properties of large arteries: results of a population-based study P. Roucka, J. Filipovsky, M. Ticha, R. Cifkova*, V. Lanska, V. Stastna 2nd Department of Internal Diseases, Medical Faculty Pilsen; * Department of Preventive Cardiology, IKEM Prague, Czech Republic Purpose of the Study: To assess the determinants of arterial stiffness and pulse wave reflection in a general population. Methods: We performed a population-based study according to the protocol of the WHO-study “MONICA”. Of 891 subjects, aged 25–67 years, randomly chosen from a population register and screened in our centre, 290 were examined with the Sphygmocor device.Aortic pulse wave velocity (PWV) and PWV on lower limbs were measured.Wave reflection was assessed from radial pulse wave analysis. Results: Aortic PWV increased with age and was similar in both sexes. PWV measured above lower extremity,i. e.above muscular type arteries, was higher in males and did not increase with age. While lower in younger females, it increased in the highest age group (55–67 years) where it reached the same value as in males. AI was higher in females in all the age groups and increased steeply with age in both sexes. Besides age, the relationship of factors of atherosclerosis to both PWV and AI were weak or non-significant. Conclusion: The steep increase of both aortic PWV and AI with age shows that these parameters reflect biological aging of arterial system. The weak associations with cardiovascular risk factors reflect the fact that the mechanisms of stiffening and of increased wave reflection are different from atherosclerosis. Supported by the grants No. NG 6757–4 and CEZ: J13/98: 111400001.

Noninvasive Measurement of Aortic Compliance as a Marker of Increased Risk of Coronary Artery Disease Richard L. Summers, MD, Alan E. Jones, MD, James C. Kolb, MD Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS 39216 Purpose of the Study: Advanced atherosclerosis typically results in reductions in aortic compliance (AC). This study examines the potential of using noninvasive measures of AC using impedance cardiography as a marker of advanced coronary artery disease (CAD) in patients presenting to the emergency department (ED) with acute chest pain. Methods: AC was calculated from noninvasive measurements of stroke volume and pulse pressure using impedance cardiography and sphygmomanometry in a convenience sample of patients presenting with acute chest pain and in whom a recent cardiac catheterization had been performed. The determined AC for each patient (corrected for age and mean arterial pressure) was compared to the graded measure of the degree of coronary disease found by catheterization (mild, moderate, severe). The sensitivity of the measured AC in predicting CAD was calculated using a cutoff level comparable to the normal average AC found in patients without disease (1.5 ml/mmHg). Results: In 42 patients studied, a stepwise correlation was found between the graded degree of CAD and the determined compliance. In those patients with minimal or moderate CAD, mean compliance was 1.0 ml/mmHg as compared to a significantly lower value of 0.59 ml/mmHg found for patients with more severe disease (p < 0.01). In all patients with CAD, 95 % of the AC values fell below the 1.5 ml/mmHg cutoff. Conclusion: Noninvasively determined AC measures might potentially be useful as a marker of CAD in patients presenting to the ED with acute chest pain.

Brachial and aortic blood pressure in a population sample: should we classify the subjects according to their central rather than peripheral pressure? M. Ticha, J. Filipovsky, *R. Cifkova, *V. Lanska, P. Roucka, V. Stastna Department of Internal Medicine II, Medical School, Pilsen; *Department of Preventive Medicine, Institute of Clinical and Experimental Medicine, Prague, Czech Republic Purpose of the Study: To address the question if one should classify hypertension according to brachial systolic BP (BSBP) or to aortic systolic BP (ASBP). Methods: Healthy subjects 25–65 yrs.of age were randomly selected and examined within the framework of a population survey. In 290 subjects (143 males and 147 females), radial pulse wave analysis, using the Sphygmocor system, was performed. This noninvasive method allows an estimate of the ASBP; repeated validation studies against invasive BP measurements showed good agreement. Results: BSBP 120 mmHg (= upper limit of optimal BP) and 140 mmHg (= lower limit of hypertension) correspond to ASBP 107 and 125 mmHg, respectively, in males; and to 108 and 130 mmHg, respectively, in females (with similar percentile distribution). The subjects were divided into three groups according to BSBP (< 120, 120–139, > 140 mmHg) as well as into three groups according to the corresponding limits of ASBP. 10.5 % of males were classified to a lower category of BSBP than of ASBP, and 7 % to a higher category of BSBP than of ASBP.In females, the values were 9.4 % and 6.8 %, respectively. When the analysis was performed separately for younger [25–45] and older subjects (46–65 years), the highest disagreement between the two classes was found in younger females (a total of 21.8 %). Conclusion: There exists a discrepancy between the classifications according to the BSBP and estimated ASBP; the latter is probably more closely related to the incidence of future cardiovascular events. When classifying according to BSBP instead of ASBP, we may underestimate the vascular risk associated with hypertension.

Insulin-resistance is an independent predictor of subclinical macrovascular involvement in mild Type 2 diabetes F. Vittone, C. Palombo, C. Morizzo, A. Natali, M. Kozàkovà, D. Baldassarre, E. Toschi, E. Ferrannini Department of Internal Medicine, University of Pisa, Italy; CNR Institute of Clinical Physiology, Pisa, Italy; Institute of Pharmacological Sciences, University of Milan Purpose of the Study: In Type 2 Diabetes (DM), macrovascular complications seem to depend mainly on lipid abnormalities. Insulin-resistance (IR) provides a unifying hypothesis accounting for the various metabolic fingerprints. To assess the role of IR in the early stage of large artery involvement in DM. Methods: 19 non-obese non-hypertensive pts with DM under hypoglycemic therapy and 10 age- and sex-matched normal controls (NL) were studied. BMI, BP and total cholesterol (TC) were similar in both groups. Insulin sensitivity was assessed by a 2-hr euglycemic hyperinsulinemic clamp (40 mU/min/m2).Carotid artery (CA) compliance was determined by continuous and simultaneous recording of CA diameter (Wall Tracking) and finger arterial pressure,and was expressed as the area under the diameter/pressure curve (AUC) over a given pressure range (70–130 mmHg). Results: Insulin-stimulated glucose uptake (M: µmol/min/per kg of free fatty mass) was 46 ± 10 in NL, and 33 ± 13 in DM (p < 0.005). Within DM pts, 11 were insulin-sensitive (IS: M-value within 2SD of the mean of NL) and 8 were insulin-resistant (M in IS vs IR pts: 41 ± 9 vs 21 ± 3, p < 0.001). IR pts had a lower AUC than IS and NL (0.315 ± 0.104, 0.481 ± 0.107 and 0.518 ± 0.188 (mm2/

3rd Int. Workshop on Noninvasive Monitoring

mmHg*10–3)*mm Hg, p < 0.02), and higher plasma triglycerides (TG: 184 ± 93, 111 ± 32 and 87 ± 47 mg/dl, p < 0.02). Plasma glucose, HbA1c, TC, and CA intima-media thickness were comparable in IS and IR. In the overall study population and in the DM group alone, in univariate analysis, AUC correlated directly with M (r = 0.61, p < 0.02) and inversely with TG and insulin (r = –0.55 and –0.51; p < 0.05 for both). By multivariate analysis, M and TG remained independently associated with AUC. Conclusion: In DM, IR appears as an independent mechanism responsible for the early subclinical derangement of large artery function

Arterial Stiffness, Wave Reflections and the Risk for Coronary Artery Disease Thomas Weber, MD*, Johann Auer, MD*, Erich Kvas, ScD**, Elisabeth Lassnig, MD*, Robert Berent, MD*, Bernd Eber, MD*, Michael F. O’Rourke, MD1 From the * Cardiology Department, General Hospital, Wels, Austria; ** Hermesoft Biostatistics, Graz, Austria; 1 St.Vincent’s Hospital, Sydney, Australia Purpose of the Study: We aimed to determine whether indices of arterial stiffness and wave reflections, derived non-invasively, could be associated with coronary atherosclerosis in clinical practice. Increased arterial stiffness, determined invasively, has been shown to predict a higher risk for coronary artery disease (CAD). Methods: We enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected CAD. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery and a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented Pressure (AP) was defined as the difference between the second and the first systolic peak, Augmentation Index (AIx) was the AP expressed as a percentage of the pulse pressure. Results: In univariate analysis, a higher AIx was associated with an increased risk for CAD (OR 4,06 for the difference between the first and the fourth quartile (CI 1.72–9.57, p < 0.01)). In multivariate analysis, after controlling for age, height, hypertension, HDL-cholesterol and medications, the association with CAD-risk remained significant. The results were exclusively driven by an increase in CADrisk in the younger patient group (up to 60 years of age). Moreover, the extent of CAD showed a statistically significant association with AIx, normalized for a heart rate of 75, and AP in the whole patient group (Spearman-R = 0.12 and 0.09, respectively), which was stronger in younger patients (Spearman-R = 0.23 and 0.17, respectively, p < 0,05). Conclusion: AIx and AP, non-invasively determined manifestations of premature arterial stiffening and increased wave reflections, are independent risk markers for CAD in men up to 60 years of age.

State of the art lectures (Abstracts received incompletely)

Ca2+ Regulation of signal transduction in the endothelium W. F. Graier Department of Medical Biochemistry and Medical Molecular Biology, University of Graz, Austria Since many years Ca2+ is known as a mediator for central and pivotal processes including muscle contraction, blood clotting and platelet

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aggregation. With recent improvements of the techniques to measure cellular Ca2+ signaling the concept of Ca2+ as a signaling molecule was further extended.Coincidently,the endothelium that was thought to represent a quiescent barrier between blood and vascular smooth muscle was discovered to serve as a regulator of vascular tone. Remarkably, all of the newly discovered paracrines are strictly controlled by endothelial Ca2+ , and, thus, a new paradigm explained the elevation of Ca2+ as the mediator for biosynthesis of the vasorelaxing prostacyclin or nitric oxide as well as the release of the vasoconstrictor endothelin-1. Today, we know that Ca2+ contributes to cytoskeleton organization and the activation of a variety of signal transduction pathways such as MAP/ER-kinase, SAP/JN-kinase, Wnt signaling and tyrosine kinases. Furthermore, Ca2+ was found to be involved in the regulation of gene expression by its effect on transcription factors like CREB or NFAT-1 and in the posttranslational modification and folding of proteins.Considering all known Ca2+-initiated/regulated/modulated processes it is hard to understand that Ca2+ paradoxically controls different even converse functions in one given cell. But how can one single molecule as simple as Ca2+ serve as a selective intracellular mediator for a multitude of cellular functions? The key to solve this apparent paradox involves a localized Ca2+ signaling machinery, a distinct distribution of Ca2+-sensitive proteins and last but not least a conceptional new Ca2+-mediated signaling pathway. Notably, such complex machinery for cellular Ca2+ homeostasis also represents an initial/early target in pathology.

Understanding autonomic cardiovascular regulation through blood pressure and heart rate variability analysis Gianfranco Parati, Paolo Castiglioni, Alberto Maronati, Marco Di Rienzo, Giuseppe Mancia Department of Clinical Medicine, Prevention and Applied Biotechnology, University of Milano-Bicocca, Milan; Cardiology II, S.Luca Hospital, Istituto Auxologico Italiano, Milan; Bioengineering Centre, Fondaz. Don Gnocchi, Milano, Italy Computer analysis of blood pressure and heart rate variability is proposed as a means to evaluate the dynamic features of cardiovascular control mechanisms both in health and disease. Indeed studies making use of this approach have offered us a considerable amount of information on the physiology of cardiovascular regulation either in a laboratory environment or in daily life conditions. These studies have also allowed us to deepen our understanding of the alterations in cardiovascular control mechanisms that may characterize a number of diseases, and on their possible changes under the effect of different types of therapeutic interventions. Technological advancement both in the techniques for signal recording and in the methods for signal processing and data analysis has led in these years to a progressive diffusion of this approach and to widening its range of applications. The introduction of spectral analysis techniques has allowed us to quantify the various frequency components that characterize blood pressure and heart rate variability. Several investigators have focussed mostly on relative fast oscillations, with periods equal to or shorter than 20–30 seconds, resulting in well-defined spectral peaks. Other investigators, making use of broad-band spectral analysis methods, have considered not only the above fast oscillations but also slower and sometimes less regular blood pressure fluctuations, spanning over a wider range of frequencies and offering a more comprehensive assessment of cardiovascular regulation. The availability of mathematical models for the simultaneous quantification of fluctuations in several biological signals and for the assessment of their mutual interactions has offered a more suitable tool for approaching the high degree of complexity that represents an intrinsic feature of cardiovascular variability. In this context, new and promising perspectives have been offered by techniques that allow us to focus on the simultaneous fluctuations in blood pres-

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sure, heart rate, respiratory activity and other biological parameters, and to quantify their reciprocal interactions. In particular, the assessment of the interaction between blood pressure and heart rate fluctuations has offered a quantification of “spontaneous” sensitivity of baroreflex control of heart rate, with no need of any external intervention on the subjects under examination. Finally, the application of the above methods in a clinical setting

has been made easier by the development of innovative techniques for non invasive beat-to-beat blood pressure monitoring, through use of finger cuffs. These techniques, in spite of some problems related to its peripheral site of measurement, have made the quantification of short-term blood pressure variations possible without the inconveniences of an intra-arterial line, which is often unsuitable in several types of patients.