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Electrocardiology

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FIELD STIMULATION OF HEART CELLS AT 37~ AND 27~ Bradley A. Stone, Melvyn Lieberman, and Wanda Krassowska Dept. of Biomed. Eng. and Cell Biology, Duke Univ., Durham, NC

POTENTIAL DISTRIBUTIONS IN A BIDOMAIN WITH REALISTIC GEOMETRY. Robert C. Penland and Craig S. Henriquez. Duke University, Dept. of Biomedical Engineering, Durham, NC

Stimulation thresholds were measured in isolated cells at 37~ and 27 ~ C and compared with theoretical predictions. Cells from 11 day old chick hearts were isolated with trypsin, incubated for 18 hours, and exposed to uniform fields of 0.4-40 ms durations. Threshold fields, Eth, were measured in 10 cells at 37~ (diam. d=20.25 43.13 #rn) and in 25 cells at 27~ (d=18.54-2.52 #m). To account for different cell diameters, thresholds were expressed as the maximum membrane potential, Vth=O.75Ethd. A chick heart cell was modeled as a sphere of d=20 #m. The fast sodium current of the membrane was represented by Ebihara-Johnson (1980) model and other currents, by Luo-Rudy (1991) model. Lowering the temperature reduced measured thresholds for all stimulus durations. Rheobase decreased from 30.2 to 21.5 mV and chronaxie increased from 0.4 to 0.8 ms. These changes were reproduced by the model when the rest potential was increased from -83 to -73.5 mV and Q10=3 was used to modify rate coefficients. (Supported by NSF grants BES-94-09026 and CDR-8622201 (B.S.,W.K.) and NIH grant HL27105 (M.L.))

Tissue geometry, anisotropy and fiber structure are believed to play an important role both in determining polarization during field stimulus and in guiding the spread of activation in cardiac tissue. We use a new finite volume formulation based on local current conservation to examine potential distributions during stimulation and activation in a realistic 2D bidomain. Our tissue model is representative of a transmural slice through the RV parallel to the basal plane in which the fibers are oriented circumferential[y around the slice. Membrane dynamics are the modified Fitzhugh-Nagumo equations. We applied both extracellular field and transmembrane stimuli to the tissue and computed the time course of potential distributions. These results were compared with those from a similar rectangular bidomain that were mapped onto the irregular grid. In the realistic case, the geometric effect on the electrical loading acts to skew the potential distributions during stimulation and activation to curve toward the endocardium. Stimulation in an unequally anisotropic bidomain with fiber and domain curvature leads to membrane polarization and activation patterns not predicted by the rectangular bidomain. This supports the hypothesis that physiologic structure is a key factor in determining the activation of cardiac tissue.

368

STIMULATIONOF CARDIAC TISSUE: SAMPLE VOLUME AND PENETRATION DEPTH Emilia Entcheva, James Eason and Fritz Claydon Department of Biomedical Engineering, The University of Memphis We examine the 3D distributionof the tmnsmembrane potential (TMP), potential gradient (PG), current density (CD) and power dissipation (PW) in a block of cardiac tissue with nominal anisolropy and moderate inwamuml relation, Constant current is injectedthrough epicardial bipolar electrodes.A finite element bidomain model is utilized for the simulations. When stimulation is applied parallel to epicardial fibers (PaEF) vs, perpendicular to epicardial fibers (PeEF) significant morphological changes are observed in the sample volume (s.v.), defined as the region enclosed by an isosurface, and penelration depth (p.d.). For stimulation PaEF vs, PeEF efl~ts can be summarized as follows: (1) the s,v. for TMP and PW increases (35% and 55%, respectively) by spreading on a bigger epicardial area without change in the p.d.; (2) the PG undergoes dramatic increase both in s.v. (110%) and p.d. (450%), and its epicardial appearance changes from elongated to a more uniform circular one; (3) the shape of the CD and PW s.v. changes from elongated to fan-like. These findings may serve as guiding informationto position electrodes in stimulation and defibrillationconditions.

371 QUANTITATIVE CHARACTERISTICS OF REENTRANT PATHWAYS DURING VENTRICULAR FIBRILLATION J.M. Rogers, J. Huang, W.M Smith, R.E. Ideker University of Alabama at Birmingham Reentrant wavefronts (RW) are thought to play a major role in governing ventricular fibrillation (VF). To determine their prevalence and characteristics in intact fibrillating hearts, we sutured a 21x24 unipolar mapping array (2 mm spacing) to the right ventricular epicardium of 7 pigs. In each animal, VF was induced 4 times and data segments 4 s long starting 1, 10, 20, 30, and 40 s post-induction were recorded. Wavefronts (W) were isolated from one another by analysis of each signal's first derivative. RW were those W that activated the same electrodes more than once. The Path traced by the tip of each RW was found by identifying the shortest path that connected electrodes activated by the RW in all time-steps. Each path included one or more closed loops (one per cycle). RESULTS. Out of 14,588 W, there were 309 RW with 448 full cycles. Mean cycle length was 93+/-23 ms. Mean cycle area (83+/-58mm2) was well below the area of the array. Cycles were roughly elliptical with mean aspect ratio 2.5+/-1.4. CONCLUSIONS. We used an objective, automatic method to search 560 s of VF for reentrant wavefronts. Such wavefronts were rare and short-lived, with most persisting for 1-2 cycles.

Poster Presentations 369 CONDUCTION BETWEEN ISOLATED RABBIT PURKINJE AND VENTRICULAR MYOCYTES D. J. Huelsing 1'2, J. M. Cordeiro 3, K. W. Spitzer 4, and A.E. Pollard 2 Tulane Univ., New Orleans, LA l, Univ. of Alabama-Birmingham, Birmingham, AL 2, University of Calgary, Calgary, Alberta, Canada s, Univ. of Utah, Salt Lake City, UT 4 Unidirectional block at the Purkinje-ventricular junction (PVJ) has traditionally been attributed to the macroscopic structure of the PVJ. In this study, though, we examined possible membrane-level contributions using single, isolated rabbit Purkinje (P) and ventricular (V) myocytes coupled by a variable resistance (Rj). Block occurred between paired V myocytes at lower Rj values during conduction from the smaller to larger myocyte (115 =t= 59 Mf~) than from the larger to smaller myocyte (201 i 51 MFt). Although P myocytes were slightly larger than V myocytes, block occurred at much lower R 3 values during P to V conduction (85 + 39 M~) than during V to P conduction (912 4- 175 Mr/). The mean membrane resistance was larger in P myocytes (98 Mfl) than in V myocytes (29 Mfl), contributing to greater P excitability and promoting V to P conduction. Further, companion computer simulations showed that P to V block occurred at lower Rj values when the transient outward current was increased or the calcium current was decreased in the model P cell, suggesting that intrinsic differences in phase 1 repolarization contribute to unidirectional block at the PVJ.

372 AUTOMATIC EKG-BASED HEART RATE ESTIMATION AND DYSRHYTHMIA DETECTION A. Bartolo, B.D. Clymer, R.C. Burgess, and J.P. Turnbull The Ohio State University, BME Center and Dept. of Elec. Eng., Columbus and The Cleveland Clinic Foundation, Dept. of Neurology, Cleveland, OH Clinical examination of patients with sleep disorders generally involves analysis of multiple biosignals recorded overnight. The electrocardiogram (EKG) is monitored to detect potentially dangerous abnormalities in the cardiac rhythm that may be associated with the disorder. Unfortunately the signal is not always examined meticulously during routine studies and dysrhythmias are often missed by the human analyst, particularly since they tend to occur sporadically. Changes in heart rate are also important indicators of heart function, however subtle changes and trends spanning several seconds are often difficult to discern from the raw EKG signal. To address these concems we have developed an EKG-based heart rate estimator which outputs heart rate data continuously in real time. The system is capable of identifying arrhythmias as well as atypical QRS complexes. It also recognizes and dismisses periods of high electromyogram activity which often occur due to patient movement. The algorithm will be used to highlight episodes of abnormal cardiac activity and enable their identification during routine sleep studies.

Electrocardiology - Posters

373 INVESTIGATION OF MECHANISMS OF ARRHYTHMIAS IN A SINOATRIAL NODE BY MATHEMATICAL MODELS I. Tipans Riga Technical University, LV- 1658 Latvia In order to investigate different mechanisms of generation of arrhythmias and also to compare different anti-arrhythmic drugs, modifications of mathematical models o f propagating action potentials in a sinoatrial region of the heart were developed. Modelling experiments were carried out for a fiber element, including the action of different calcium channel blocking drugs, with kinetic binding and unbinding parameters, determined from experimental results. Critical concentrations were determined, when the circulating excitation wave disappeared. Created models were used to investigate main mechanisms of arrhythmias, connected with the circular excitation wave in a limited region, appearance o f oscillations after normal action potentials, elevated automaticity o f cells. Corresponding values of parameters were determined in a modelling experiment. Mathematical methods &analysis of oscillations in a phase plane were applied to determine stable limiting cycles and corresponding values of parameters of such system, i.e. to determine conditions when transmembrane potential oscillations occur.

374 HEART RATE AND HEART RATE VARIABILITY IN MALE BROILERS AT RISK FOR SUDDEN DEATH SYNDROME Susan M. Blanchard, Dennis K. Dewolf, Tagbo C. Ekwueme-Okoli, Laurel A. Degernes, James D. Garlich North Carolina State University, Raleigh, NC Sudden Death Syndrome in poultry is increasing in frequency and can lead to the deaths of 2-4% of birds in a male broiler flock. An underlying cardiovascular mechanism that may involve arrhythmias and may be related to rapid growth is suspected. Six 2-week old male broilers (409_+11 gm) had transmitters implanted subcutaneously in their coelomic cavities. The birds were kept in individual cages and subjected to 23 hours of light and one hour of darkness, a regimen followed in most commercial broiIer houses to encourage constant eating. The birds weighed 930_+30 gm when 3 weeks old. ECGs (1 rain at 1000 samples/s) and temperature (T) were recorded every 15 rain and were analyzed in birds 16-22 days old. Heart rate (HR) and heart rate variability (HRV) were measured for three 10-beat periods during each l-rain sample. Power spectra (PS) were determined for each l-rain ECG. The effects of light and dark periods on HR, HRV, PS, and T were evaluated. Supported by the NC Agricultural Research Service and NSF grant BIR-9634022.

375 THE EFFECTS OF CYTOSKELETAL REORGANIZATION ON THE PROBABILITY OF STRETCH-INDUCED ARRHYTHMIAS IN MATURE RABBIT HEART K.K Parker*, L.K. Taylor#, J. Wray, J. Atkinson##, J.P. Wikswo*, Jr., D.E. Hansen# Vanderbilt University, Depts. of Physics*, Medicine#, and Pathology## Stretch-activated channels (SACs) have been identified as transducers of mechano-electric interaction in the heart, where they may play a role in arrhythmogenesis. Transmission of mechanical stresses to SACs by cytoskeletal attachments has been hypothesized. We studied the arrhythmogenic effects of stretch in 11 Langendorff-perfused rabbit hearts in which we pharmacologically manipulated the microtubular network of the cardiac myocytes. Group 1 (n=6) was treated with colchicine, which depolymerizes microtubules, and Group 2 (n=5) was treated with taxol, which po[ymerizes microtubules. Stretch-induced arrhythmias (SIAs) were produced by transiently increasing the volume of a fluid-filled left ventricular (LV) intracavitary balloon with a volume pump driven by a stepper motor. Electrical events were recorded by a contact electrode which yielded high fidelity recordings of monophasic action potentials and stretch-induced depolarizations. The probability of eliciting an SIA increased (0.186 +/- 0.070 to 0.600 +/- 0.197, p=0.002) in hearts treated with taxol, whereas hearts treated with colchicine showed no change. We conclude that proliferation of microtubules increases the arrhythmogenic effects of transient LV diastolic stretch.

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376 A 3D FEM BIDOMAIN MODEL FOR DEFIBRILLATION Qiuju Huang and Frank J. Claydon Dept. of Biomedical Engineering, The University of Memphis The objective of this study is to develop, for the first time, a 3D FEM bidomain model to simulate the cardiac transmembrane potential (TMP) induced by a defibrillation shock. The inhomogeneities of the torso are modeled as eccentric spherical shells with both cardiac fiber curvature and rotation incorporated. The numerical computation of the model is validated by an analytic solution. The TMP induced by transthoracic and transvenous defibrillation fields are simulated and visualized. The percentage distribution of TMP in the myocardium is plotted (solid line) in the figure below for transvenous electrodes. The dotted line is the TMP distribution for the same shock with reversed electrode polarity. The two curves differ from each other by 300 28.6% RMS error. This is consistent with results presented by Trayanova in a 2D bidomain study. In particular, our results support Trayanova's conclusion that reversed electrode polar40 -20 O 20 40 r~m .,,V, percentage of myocardium above threshold ity may reduce the DFT.

377 SHOCKS C(K]RDINATED WITH THE DEPOI.ARIZ]NG PHASE (POSHIVE UPWARD / NEGATIVE DOWNWARD) OF THE VF WAVEFORM IMPROVES DEFIBRHJ ATION EFFICACY SANDEEP NAIK, DENNIS MENDOZA, PENG-WIE HS[A, PH.D. VIRGINIACOMMONWEALTH UNIVERSITY,RICHMOND, VA ~ o n

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filxillation~/F) wavefonn in a dosed dest c~me ~ (n=8). An ilegrated endocardial catheter compri~g ofa s t ~ r vma cava, an RV springoN and an RV lip was inserted ~ ~e c ~ j u ~ v ~ ~xicr tt~osco~c ~ c ~ w~e ~ ac~ve C ~ w s phced in the loll peclomlarea A ~ shock at 50 % successdeficm]lNonenergy [RV coil (+) ~-~Can (-)] was laSggeredafter a [x'edo.em-~ W kamrA and the "o,rav~nn was sm~edufingoo~giwafionRV tip (-) 4->Can (+). Slxzckswere eh~iffedinto o~e of the two phases, depolarizingor r e p o ~ phase. The d e p o l a ~ phase was defined as ~aer upwaxdsignalon the podtive VF voltageor down,a ~ ~gnalon the negage VF voltage. RESULTS : In 80 defiNfllafion~ p e r f o r ~ 51 (64%) suco~ededwhile 29 06 %) failed. Shocks coinddmt on the depolarizationphase had higherpm&~ty of mmess as compared to repohriz~on phase (60 + 8.2 % vs. 40 + 82 %, p< 0.02). This study demons~oa th,atstxr,ks coordimtedwiththe pofitiveupward/ n e g a ~ dox,mward region of the VF waveformimprovedeh'bn]lafionefficacy.

378 TRANSVENOUS DEFIBRILLATION IN A REALISTIC HUMAN HEART: TRANSMEMBRANE PATTERNS Emilia Entcheva, Amy de Jongh and Fritz Claydon Department of Biomedical Engineering, The University of Memphis This study was designed to examine the changes in the transmembrane potential (TMP) resulting fi'om transvenous defibrillation. The model was conslmcted from 90 lransverse MRI slices of a human torso. An unslructured (Delaunay) tessellation technique was used to construct the mesh. A 3D finite element bidomain model was applied to directly compute the TMP arising from the defibrillation shock. Two electrode configurations were tested: RV--~Can* and RV--,,.SVC +with the RV electrode touching the free wall, The epicardium around the SVC orifice was directly depolarized by the SVC electrode, and a small (34cm2) hy~qx)larized regaon was present laterally to it. Epicardial breakthrough hyperpolanzation was present with depolarized areas towards the apex and the base. These effects were less pronounced for the configuration with the can, where the polarization was concenlrated at the left side of the heart and the apex. Our results suggest that for wansvenous defibrillation other mechanisms (virtual electrode effects) might work in parallel with the the field induced polarization, as shown recently by Efunov (PACE'W, vol.20, p. 1080) in a rabbit heart.

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Electrocardiology - Posters

379 ATTEMPTS AT NONINVASIVE ULTRASOUND-INDUCED CARDIAC DEFIBRILLATION Bruce C. Towe, Ph.D, Raymond Rho, Christopher Cooney Bioengineering Program, CBME Dept. Arizona State University This work investigates the possibility of using high energy ultrasound as a way of bioelectrically stimulating and possibly defibrillating the heart. Special high energy ultrasound transducers were developed using an electromagnetic-acoustic principle. They were capable of peak pulse pressures in the range of 10 MPa for 50 microseconds at about 100 kHz. Also constructed were piezoelectric transducers capable of 1-3 MPa at 70 kHz with variable pulse durations of 1-100 milliseconds. These transducers were applied to adult pig hearts' exposed by thoracotomy and the resulting bioelectric responses of the heart recorded from multichannel epicardial electrograms. Optimal ultrasound pulse durations for cardiac bioelectric excitation were in the range of 3-5 milliseconds. Pacing of the heart could be easily achieved at moderate pulsed ultrasound power levels when the pizeoelectric transducer was applied to the heart. Transthoracic cardiac bioelectric stimulation was achieved with more difficulty but was possible in some animals when using EMAT transducers. Atrial defibrillation was occasionally but not reproducibly observed with the EMAT transducer on the exposed pig heart.

380 SPECTRAL AUTOCORRELATION BETWEEN ECG DURING VF 1S CORRELATED WITH PROBABILITY OF DEFIBRILLATION A.R. Patwardhan, S.A. Moghe, K. Wang, and F.M Leonelli. University of Kentucky, Lexington, KY 40506. We investigated whether the correlations between oscillations at different frequencies in orthogonal ECGs recorded during ventricular fibrillation (VF) were associated with defibrillation shock (DS) outcome. Orthogonal ECGs were recorded during 15 sec of electrically induced VF which was followed by a DS with 50% probability of successful termination of VF. The DS were delivered between a right ventricular apical coil and a subcutaneous patch electrode. Spectral autocorrelation functions were estimated from 4 sec of data just prior to delivery of DS. Of the 485 trials in 11 dogs, 236 were successful (49%) and 249 were failures (51%). Spectral autocorrelations within (86-11.7,86-11.7) Hz bandwidth were 10-15% higher for unsuccessful than successful trials (p < 0.02). Recently proposed wandering wavelet and Doppler hypothesis of VF suggests that increased spectral autocorrelations for unsuccessful trials may be due to increased non-stationarity of the activation core. Supported by 7he

WhitakerFoundation.

382 MUTATIONS IN CARDIAC POTASSIUM RESPONSIBLE FOR LONG QT SYNDROME M.A. Choma and A.M. Brown

CHANNELS

Long QT syndrome is associated with mutations in the gene for the cardiac potassium channel human ether-a-go-go (HERG). Acquired long QT syndrome is much more common and is associated with the ingestion of cardioactive drugs. It is hypothesized that acquired long QT syndrome is caused by mutations in HERG. I will test this hypothesis by examining the effects of a commonly used cardioactive drug, quinidine, and several commonly used nonsedating antihistamines which have been reported to be cardiotoxic (loratidine, cetirizine and ebastine) upon the function of HERG. Wild-type and known mutations of HERG will be expressed in Xenopus oocytes and mouse L-cells. The function of the channel will be assayed through two microelectrode voltage clamp measurements of channel currents. Dose-response curves for the various drugs will be compared between wild-type and mutated channels. If the wild-type and mutated channels are affected differently by the cardiotoxic and cardioactive drugs, we will have evidence for a congenital predisposition to acquired long QT syndrome. Because these drugs are so widely used, such a predisposition would have widespread implications on the treatment of cardiovascular disease.

383 AUTOMATIC DETECTION OF ATRIAL ACTIVITIES BY ESOPHAGEAL LEAD H. W. Chiu, S. H. Lee, T. Kao, H. C. Hsiao*, C F. Kong* Institute ofBME, Yang-Ming University, Taipei, Taiwan. Division of Cardiology, Veterans General Hospital, Taipei, Taiwan.* Generally, the RR intervals on surface ECG (S-ECG) are the time series data for heart rate variability (I-IRV) analysis because automatic detection of R-waves from S-ECG is easy and well-developed However, the RR intervals are not proper HRV data for AV-block patients. The P-waves are difficult to be detected and located precisely from S-ECG. Therefore, we developed a method to detect P-wave location automatically from the esophageal ECG (E-ECG) in this study. Both E-ECG and S-ECG (lead II) were recorded simultaneously. R-waves detection on S-ECG was performed by finding the local extremes satisfying some amplitude and slope thresholds. By the same algorithm, all P-waves and R-waves on EECG could be obtained without distinction. The P-waves are extracted out by the cancellation of R-waves on E-ECG and those on S-ECG. The correlation coefficient between PP intervals derived from E-ECG by our method and AA intervals obtained from intra-atrial lead exceeds 0.96 on normal subjects and AV-block patients. MEDICAL IMAGING

Cardiovascular Imaging 381 LAPLACIAN ELECTROCARDIOGRAMS WITH ACTIVE TRIPOLAR CONCENTRIC SENSORS C.C.LU and P.P.Tarjan Department of Biomedical Engineering, University of Miami Coral Gables FL 33146

384 TIME RESOLVED LASER-INDUCED FLUORESCENCE FOR CLASSIFICATION OF ATHEROSCLEROTIC LESIONS J.M. Maarek, L. Marcu, and W.S. Grundfest. Dept. of Biomcd. Eng., Univ. Southern California. Los Angeles, CA.

A tripolar concentric ring(TC) sensor was developed with a uniquely AC coupled instrumentation amplifier(IA) to improve the signal to noise ratio(SNR) of the Laplacian electrocardiogram(LECG) signal. A high degree of selectivity is achieved as the three closely spaced concentric rings provide spatial differentation and common mode rejection(CMR). The amplifier is mounted directly above the sensor to minimize the interference. The high CMR of the TC sensor and the amplifier results in a TC sensor that can acquire high SNR LECG signal. No further digital signal processing is required. The very high input impedance of the IA renders the sensor insensitive to fluctations in the skin electrode's impedance. Skin preparation is not necessary. The amplifier has a total gain of 1000 with a pass band from 5Hz to 500Hz. Twenty five seconds of LECG and lead II ECG were collected from eight subjects. ECG's Rwave served as a time reference to compare the peaks from the LECG. Different time delay patterns for different measuring site were observed. Time delay changes between a nomal sinus rhythm and an abnormal one were observed in one subject with a bigeminal ECG waveform.

We measured the spectro-temporal fluorescence emission (337 nm excitation, 3 ns pulse) of 37 excised aortic samples ranging from normal to type V atherosclerotic lesion (AHA classification). The emission transients between 370 and 510 nm were deconvuluted from the excitation (Laguerre expansion of kernels) and fitted with a double exponential to characterize the fluorescence decay. Decay time constants and intensity ratio (R = 1470/1390) were correlated with histulogic classification of the samples (H&E staining). Decay constants Xl (fast) and x2 (slow) increased with lesion severity from "~l= 1.2 _+0.1 ns, x2= 5.4 + 0.2 ns for normal samples to x~= 1.5 + 0.1 ns, x2= 6.8 + 0.1 ns for type V lesions (390 rim, p < 0.05). Decay constants at 390 nm and ratio R predicted sample classification between near-normal (normal - type I), early disease (type H), and disease (type III- type V) with 90% accuracy (discfiminant analysis) suggesting that time-resolved fluorescence spectroscopy could be used to characterize atherosclerosis in-situ.