Eur J Appl Physiol (2007) 100:185–191 DOI 10.1007/s00421-007-0415-x

O RI G I NAL ART I C LE

Assessment of cardiac contractility during a cold pressor test by using (dP/dt)/P of carotid artery pulses Kayo Moriyama · Hirotoshi Ifuku

Accepted: 30 January 2007 / Published online: 24 February 2007 © Springer-Verlag 2007

Abstract The ratio of the Wrst derivative (dP/dt) of a carotid artery pulse to the developed pressure (P), (dP/ dt)/P, is an easily measurable, noninvasive index of cardiac contractility even in moderate exercise. We examined the eVects of transient cold exposure on cardiac contractility in normal reactors (n = 12) and hyperreactors (an increase in systolic or diastolic pressure >15 mm Hg; n = 6) by using this index. Eighteen healthy participants were subjected to the cold pressor test, which required them to immerse the right hand in chilly water (4°C) for 2 min. Although cold stress maximally increased mean blood pressure during the second minute, it maximally increased heart rate and cardiac contractility after 60 s of immersion in both groups of subjects. Comparing normal reactors and hyperreactors by two-way ANOVA revealed a group £ time interaction for heart rate but not for cardiac contractility. These Wndings suggest that the increase in cardiac contractility during cold-water immersion dose not reXect the levels of heart rate and muscle sympathetic nerve activity, and that the speciWc responses of cardiac function to a cold pressor test in hyperreactors depends on heart rate rather than cardiac contractility.

K. Moriyama Graduate School of Education, Kumamoto University, Kumamoto 860-8555, Japan H. Ifuku (&) Department of Physical Education, Faculty of Education, Kumamoto University, Kumamoto 860-8555, Japan e-mail: [email protected]

Keywords Carotid artery pulse · Heart rate · Hyperreactor

Introduction The cold pressor test, Wrst reported by Hines and Brown (1936), is used to assess neural control of the cardiovascular system by observing the pressor response during the immersion of one hand in chilly cold water. This pressor response is induced by increased cardiac output (Briggs and Oerting 1993; Hejl 1957; Yamamoto et al. 1992) and by enhanced sympathetic nerve activity (Hines and Brown 1936; Cummings et al. 1983, Wood et al. 1984; Green et al. 1965). By muscle sympathetic nerve activity (MSNA), Yamamoto et al. (1992) showed that increased cardiac output elevates blood pressure during the initial period (0–30 s) of the cold pressor test, whereas increased MSNA plays a role during the later period (30–120 s). No study has evaluated cardiac contractility during a cold pressor test. We have reported that the ratio of the maximal rate of pressure rise (dP/dt) in carotid artery pulse to the developed pressure (P), (dP/dt)/P, is a noninvasive index of cardiac contractility even in moderate exercise, and that it reXects cardiac sympathetic nerve activity (Ifuku et al. 1994). In the present study, we examined the eVects of the cold pressor test on cardiac contractility by this index. Two large, long-term prospective studies using survival analysis have deWned blood pressure hyperreactors to the cold pressor test as individuals who respond with a rise of 15 mm Hg or greater in their systolic and/ or diastolic blood pressure (Kasagi et al. 1995; Menkes

123

186

Eur J Appl Physiol (2007) 100:185–191

et al. 1989). The hyperreactors have a higher incidence rate of hypertension than normal reactors. Therefore, hyperreactors may yield speciWc cardiovascular responses to the cold pressor test and in the present study a separate analysis was made for hyper- and normal reactors.

peak P

P

100 mmHg

peak d P /dt

1000

dP/dt

mmHg/s -1000

Methods

0.1 2

d P /dt

Subjects Eighteen healthy subjects (9 male, 9 female) aged 19– 24 years (21.8 § 1.3, mean § SD) volunteered for this study (Table 1). The experimental procedures were approved by our institutional committee for the protection of humans in research, and written informed consent was obtained from each subject prior to participation. All subjects were normotensive (<140/ 90 mm Hg) with no medical history of circulatory disorders; their electrocardiogram (ECG) and carotid artery pulse contour were normal.

2

mmHg/ms2

-0.1

R-R

1 mV

ECG

1s

Fig. 1 Example of the carotid artery pulse pressure (P), the Wrst derivative of the carotid artery pulse pressure (dP/dt), the second derivative of the carotid artery pulse pressure (d2P/dt2), and the electrocardiogram (ECG) trace at rest. The (dP/dt)/P was calculated by dividing peak dP/dt by peak P

Carotid artery pulse and (dP/dt)/P

Blood pressure and heart rate

Carotid artery pulse was recorded by a device described by Ifuku et al. (1993). In brief, a pulse transducer (45259, NEC San-ei) Wxed on the apparatus (originally a brace to Wx the cervical vertebrae) was held over the right carotid artery, and the subjects were allowed to swallow to relieve any discomfort from wearing the apparatus. Peak values of P and dP/dt were measured in millimeters of mercury and in millimeters of mercury per second, respectively (Ifuku et al. 1993), and (dP/dt)/P (per second) was calculated beat by beat (Ifuku et al. 1994) (Fig. 1). The onset of upstroke of P was derived from an appearance of peak value of d2P/dt2. The (dP/dt)/P was expressed as the average of heart beats every 30 s.

Blood pressure and heart rate were measured using an automated machine (STBP-780, Colin, Aichi, Japan). At a 1-min interval throughout the experiments, blood pressure was measured during the second half (30– 60 s) of each minute. Mean blood pressure (MBP) was deWned as one-third of the pulse pressure plus the diastolic blood pressure. The R–R intervals of the ECG were measured from bipolar chest leads, and the instantaneous heart rate was calculated by multiplying the inverse of the R–R intervals by 60 s. The heart rate was expressed as the average over 30 s.

Table 1 Physical characteristics of the subjects

Age (years) BMI (kg/m2) SBP (mm Hg) DBP (mm Hg) MBP (mm Hg) HR (bpm) (dP/dt)/P (/s)

Males (n = 9)

Females (n = 9)

21.7 § 1.2 22.4 § 2.4 116.7 § 8.7 70.2 § 8.1 85.7 § 7.2 63.3 § 7.8 15.2 § 3.3

22.0 § 0.9 21.3 § 3.6 110.1 § 8.4 71.0 § 7.2 84.0 § 7.2 67.6 § 7.8 15.6 § 4.8

Data are mean § SD. BMI body mass index, SBP systolic blood pressure, DBP diastolic blood ressure, MBP mean blood pressure, HR heart rate in a sitting position

123

Stroke volume, cardiac output, and total peripheral resistance (TPR) Thoracic impedance (
Z) was recorded by using an impedance plethysmograph (4134, NEC San-ei, Tokyo, Japan). Two electrodes separated by at least 3 cm were placed on the neck, and two other electrodes were placed on the trunk at the level of the xiphisternum and on the abdomen. When the subjects exhaled in an ordinary way for 2 s and then held the breath for 3 s without bearing down at 55–60 s of each minute,
Z and the Wrst derivative of the impedance wave (dz/dt) were measured. At the same time, the left ventricular ejection time was measured on carotid artery pulses. Stroke volume was calculated according to Kubicek et al. (1970) and was expressed as the average of three

Eur J Appl Physiol (2007) 100:185–191

successive heart beats. Cardiac output was calculated by multiplying the stroke volume by the heart rate, and the TPR by dividing the MBP by cardiac output. The stroke volume, cardiac output, and TPR during cold stress were expressed relative to the baseline values (the average values obtained for the Wrst 5 min of the 10 min rest). The carotid artery pulse, ECG, and
Z were recorded on a DAT data recorder (RD-135, TEAC, Tokyo, Japan). After the experiments, they were replayed and led to a laboratory-oriented microcomputer (eMac, Apple, California, USA) and analyzed with Chart v5 (AD Instruments Japan, Aichi, Japan) based on MacLab (4s, AD Instruments Japan). Cold and pain sensation Both cold and pain sensations were evoked during cold-water immersion. Cold sensation was evaluated on an interval scale of 7 steps (1. very cold, 2. cold, 3. slightly cold, 4. neutral, 5. slightly warm, 6. warm, 7. hot), whereas pain sensation was on an interval scale of 4 steps (1. very painful, 2. painful, 3. slightly painful, 4. no pain) (Inoue et al. 2002). The degrees of cold and pain sensations were asked every 30 s during the coldwater immersion. Experimental procedures Preliminary experiments were carried out to familiarize the subjects with the procedures. Sudden noises were avoided during the experiments so as not to irritate the sympathetic nervous system. The subjects were instructed not to eat any food for at least 2 h before the experiments. After resting in a sitting position for 10–20 min, the subjects underwent the cold pressor test. The test was conducted according to the Hines and Brown (1936). The experimental protocol was as follows; the subjects rested for 10 min, immersed their right hands in cold water (4°C) for 2 min, and then rested to recover for 3 min. The room temperature was 23.7 § 0.4°C (mean § SD).

187

cold pressor test was measured. Then the diVerences in blood pressure between the two states were calculated. Statistical analysis The average of the data obtained for the Wrst 5 min of the 10 min rest was deWned as the baseline value. The absolute changes in (dP/dt)/P, heart rate, and MBP, and the changes in stroke volume, cardiac output, and TPR from the baseline values were sequentially calculated before, during, and after immersion of the hand in cold water. To observe time courses of changes in all measurements during the cold pressor test in both normal reactors and hyperreactors, a Dunnett’s test was performed to detect any signiWcant diVerences between mean value obtained for the last 5 min of the 10 min rest (the control resting value) and value obtained at a given time. To identify diVerences in response pattern between normal reactors and hyperreactors, these data were statistically analyzed by a 2 (group) £ 2 (time) ANOVA with repeated measures. When a signiWcant group £ time interaction was detected, a main eVect test as Post hoc analyses was performed to determine where the diVerences occurred between normal reactors and hyperreactors. To observe time courses of changes in cold and pain sensations during cold-water immersion in both normal and hyperreactors, a Steel’s test was performed to detect any signiWcant diVerences between the control value and the value obtained at a given time. Moreover, a Mann–Whitney’s U test was performed to determine where the diVerences occurred between normal reactors and hyperreactors. A P value of less than 0.05 was considered signiWcant and data were presented as means § SEM, except for cold and pain sensations, which were expressed as median (range).

Results The hyperreaction was observed in 6 of the 18 subjects (33.3%). Responses of MBP to cold pressor test

Blood pressure hyperreactors Blood pressure hyperreactors were deWned as individuals responding to the cold pressor test by an increase of 15 mm Hg or greater in their systolic and/or diastolic blood pressure during the Wrst minute of the test (Kasagi et al. 1995). To Wnd the hyperreactors, blood pressure was measured and averaged for 10 min at the resting state, and the value at the Wrst minute of the

In normal reactors, the MBP increased from the control resting value by 4.3 § 1.5 mm Hg at 60 s (P = 0.024) and by 15.0 § 1.5 mm Hg at 120 s (P < 0.001) of immersion in cold water, and by 5.9 § 1.3 mm Hg 60 s (P = 0.001) after the end of immersion (Table 2; Fig. 2). In hyperreactors, the MBP increased from the control value by 19.6 § 1.3 mm Hg at 60 s, by 25.9 § 3.1 mm Hg at 120 s of immersion in

123

¡0.5 § 0.2 ¡1.6 § 1.2 3.3 § 1.7 ¡0.6 § 0.1 ¡0.6 § 1.2 Data are mean § SEM. ***, **, * DiVerent from the control resting value (5–10 min): P < 0.001, P < 0.01, P < 0.05, respectively

¡0.8 § 0.3 ¡3.3 § 0.7 2.2 § 2.4 ¡0.6 § 0.3 ¡2.8 § 0.9 0.8 § 0.3 3.9 § 3.5 1.8 § 0.7* 17.2 § 5.8** 2.2 § 0.4** 23.6 § 6.1*** 18.3 § 1.3*** 0.1 § 0.1 0.2 § 0.6 ¡1.3 § 0.6 Hyperreactors (dP/dt)/P (/s) Heart rate (bpm) MBP (mm Hg)

1.5 § 0.3 16.8 § 5.6**

1.4 § 0.7 11.0 § 4.8 24.6 § 3.1***

¡0.7 § 0.3 ¡3.6 § 1.0 8.3 § 2.7***

0.5 § 0.5 0.0 § 0.7 0.7 § 0.4 ¡1.2 § 0.5 ¡0.4 § 1.6 0.6 § 0.6 ¡0.4 § 1.0 1.2 § 0.4 0.0 § 1.3 1.7 § 0.5* 6.9 § 1.6*** 2.0 § 0.5* 10.8 § 2.2*** 2.8 § 1.6* ¡0.1 § 0.2 0.4 § 0.4 ¡1.5 § 0.7 Normal reactors (dP/dt)/P (/s) Heart rate (bpm) MBP (mm Hg)

1.7 § 0.5* 8.6 § 2.5***

1.5 § 0.5 4.2 § 0.9 13.5 § 1.7***

0.6 § 0.5 ¡1.3 § 0.4 4.4 § 1.5**

150 s 120 s 90 s 60 s 30 s 120 s 90 s 60 s 30 s 5–10 min

Recovery Cold-water immersion Control

Table 2 Changes in (dP/dt)/P, heart rate, and mean blood pressure (MBP) during a cold pressor test in normal reactors and hyperreactors

123

0.4 § 0.4 ¡0.9 § 0.8 ¡1.0 § 1.2

Eur J Appl Physiol (2007) 100:185–191

180 s

188

Fig. 2 Changes in (dP/dt)/P, heart rate (HR), and mean blood pressure (MBP) during the cold pressor test. Data are mean § SEM. Solid circles normal reactors, open circles hyperreactors. The frame indicates the period of cold-water immersion. ***, **, and *, diVerent from the control resting value (5–10 min) at P < 0.001, P < 0.01, and P < 0.05, respectively. 999, 99, and 9, diVerence between normal reactors and hyperreactors at a given time at P < 0.001, P < 0.01, and P < 0.05, respectively

cold water, and by 9.6 § 2.8 mm Hg at 60 s after the end of immersion (P < 0.001). Heart rate In normal reactors, the heart rate increased from the control resting value by 8.2 § 2.3 beats min¡1 at 30 s, by 10.4 § 2.0 beats min¡1 at 60 s, and by 6.5 § 1.5 beats min¡1 at 90 s of the immersion (P < 0.001) (Table 2; Fig. 2). In hyperreactors, the heart rate increased from the control resting value by 16.6 § 5.2 beats min¡1 at 30 s (P = 0.006), by 23.5 § 5.9 beats min¡1 at 60 s (P < 0.001), and by 17.1 § 5.7 beats min¡1 90 s (P = 0.005) of the immersion. A group £ time interaction was observed (P < 0.001), indicating a diVerent time course of the heart rate between the two groups. Moreover, simple eVect tests revealed main eVects for the group at 30 s (P = 0.012), 60 s (P < 0.001), 90 s (P = 0.002), and 120 s

Eur J Appl Physiol (2007) 100:185–191

189

(P = 0.040) of the immersion in cold water, indicating that the heart rate was larger in hyperreactors than in normal reactors during the cold-water immersion. (dP/dt)/P In normal reactors, the (dP/dt)/P increased from the control resting value by 1.9 § 0.6 s¡1 at 30 s (P = 0.043), by 2.1 § 0.6 s¡1 at 60 s (P = 0.014), and by 1.9 § 0.6 s¡1 at 90 s (P = 0.038) of the immersion in cold water (Table 2; Fig. 2). In hyperreactors, the (dP/dt)/P increased by 2.1 § 0.3 s¡1 at 60 s (P = 0.002) and by 1.6 § 0.6 s¡1 at 90 s (P = 0.023) of the cold-water immersion. No group £ time interaction was detected (P = 0.091), indicating that there was no diVerent time course of the (dP/dt)/P between the two groups. The changes in the (dP/dt)/P were, however, larger in normal reactors (0.7 § 0.4 s¡1) than in hyperreactors (¡0.8 § 0.3 s¡1) 120 s after the end of immersion (P = 0.038, Student’s t test). Stroke volume, cardiac output, and TPR In normal reactors, the TPR increased by 20.7 § 5.0% at 120 s of hand immersion (P < 0.001) (Table 3). However, no changes from the control resting value were noted in stroke volume or cardiac output (P > 0.05). In

hyperreactors, there were no changes from the control resting value in the stroke volume, the cardiac output, or TPR (P > 0.05). Moreover, group £time interactions were not detected (P > 0.05), indicating that there were no diVerent time courses of the stroke volume, the cardiac output, and the TPR between the two groups. Cold and pain sensation The score of cold sensation in normal reactors decreased from the control value to 2 (1–3) at 30 s, to 1 (1–3) at 60 s, to 1 (1–2) at 90 s, and to 1 (1–3) 120 s of immersion (P < 0.01) (Table 4). In hyperreactors, the score decreased from the control value to 1 (1–2) at 30 s, to 1 (all at 1) at 60 s, to 1 (1–2) at 90 s, and to 1 (1– 2) at 120 s of immersion in cold water (P < 0.01). However, there was no diVerence between normal and hyperreactors (P > 0.05). The score of pain sensation in normal reactors decreased from the control value to 3 (1–4) at 30 s, to 2 (1–3) at 60 s, to 1 (1–4) at 90 s, and to 1 (1–4) at 120 s of immersion (P < 0.01) (Table 4). In hyperreactors, the score decreased from the control value to 1.5 (1–2) at 30 s, to 1 (all at 1) at 60 s, to 1 (1–2) at 90 s, and to 1 (1–2) at 120 s of immersion in cold water (P < 0.01). The pain sensation was stronger in hyperreactors than in normal reactors at 60 s during immersion in cold water (P = 0.014).

Table 3 Changes in stroke volume, cardiac output, and total peripheral resistance (TPR) during a cold pressor test in normal reactors and hyperreactors

Normal reactors Stroke volume Cardiac output TPR Hyperreactors Stroke volume Cardiac output TPR

Control

Cold-water immersion

Recovery

5–10 min

60 s

120 s

60 s

120 s

180 s

0.99 § 0.01 1.00 § 0.01 0.98 § 0.01

0.96 § 0.04 1.07 § 0.05 1.00 § 0.05

0.98 § 0.06 1.00 § 0.03 1.19 § 0.05***

1.02 § 0.03 1.00 § 0.02 1.06 § 0.03

1.04 § 0.03 1.01 § 0.03 1.00 § 0.02

0.98 § 0.04 0.99 § 0.03 1.00 § 0.02

1.00 § 0.02 0.99 § 0.01 1.01 § 0.02

0.87 § 0.04 1.13 § 0.08 1.09 § 0.08

0.98 § 0.09 1.13 § 0.09 1.18 § 0.10

1.11 § 0.05 0.95 § 0.07 1.18 § 0.13

1.12 § 0.04 0.98 § 0.07 1.10 § 0.12

1.07 § 0.04 1.02 § 0.03 1.02 § 0.04

Data are mean § SEM. *** DiVerent from the control resting value (5–10 min): P < 0.001 Table 4 Changes in cold and pain sensations during a cold pressor test in normal reactors and hyperreactors Control

Normal reactors Cold sensation Pain sensation Hyperreactors Cold sensation Pain sensation

Cold-water immersion 30 s

60 s

90 s

120 s

4 4

2 (1–3)** 3 (1–4)**

1 (1–3)** 2 (1–3)**

1 (1–2)** 1 (1–4)**

1 (1–3)** 1 (1–4)**

4 4

1 (1–2)** 1.5 (1–2)**

1 (all 1)** 1 (all 1)**9

1 (1–2)** 1 (1–2)**

1 (1–2)** 1 (1–2)**

Data are median (range). ** DiVerent from the control value: P < 0.01 9 DiVerent between normal reactors and hyperreactors at a time indicated: P < 0.05

123

190

Discussion The (dP/dt)/P of the carotid artery pulse increases during head-up tilt, cold stress, and exercise, and it reXects sympathetic nerve activity, representing a noninvasive index of cardiac contractility even during moderate exercise (Ifuku et al. 1994). Using this index, the present study examined the detailed eVects of a cold stress on cardiac contractility in normal and hyperreactors. The (dP/dt)/P increased from the control resting value during hand immersion in cold water in both groups of subjects. However, the time course of this index was diVerent from those of blood pressure. The MBP increased maximally at 120 s of immersion and maintained to be elevated until 60 s after the immersion, whereas the (dP/dt)/P increased maximally after 60 s and returned to the control resting value after 120 s. This Wnding suggests that the cardiac contractility contributes to the early pressor response to immersion together with the increase in cardiac output followed by the rise of heart rate (Yamamoto et al. 1992), but that it does not contribute to the late pressor response. In spite of a substantial increase in MBP during the cold pressor test, MSNA remains unchanged during the Wrst 30 s, and then increases to a maximum during the second minute (Victor et al. 1987) or after 60–90 s (Yamamoto et al. 1992), suggesting that MSNA is not under control of the arterial baroreceptor reXex. Although the increase in MBP reached a maximum at 120 s of cold-water immersion, the heart rate and the (dP/dt)/P increased to a maximum after 60 s in both groups of subjects. This Wnding suggests that an inhibitory inXuence of baroreceptor reXex on sympathetic outXow was not strong enough to override the heart rate or the (dP/dt)/P in the Wrst minute of cold-water immersion (Victor et al. 1987; Yamamoto et al. 1992). Despite of the maximal increase in MBP at 120 s of immersion, the heart rate and the (dP/dt)/P declined from their peak values and returned to the control resting values at 120 s of immersion. Thus, the increase in MBP appeared to inhibit heart rate and (dP/dt)/P through arterial baroreXex, which may be reset to control the new heart rate and blood pressure at 120 s of immersion (Raven et al. 2006), suggesting that cardiac function, i.e., inotropic and chronotropic actions, were under arterial baroreceptor reXex control at 120 s of cold-water immersion. Moreover, the diVerential time courses of the (dP/dt)/P and the MSNA suggest the existence of tissue-speciWc sympathetic outputs to heart or skeletal muscle which could be mediated by premotor neurons (Morrison 2001).

123

Eur J Appl Physiol (2007) 100:185–191

The (dP/dt)/P and heart rate followed almost the same time course; an increase during cold-water immersion, and return to the control resting value immediately after the end of immersion. However, comparing normal and hyperreactors, a group£time interaction was detected for the heart rate but not for the (dP/dt)/P. Thus, heart rate, but not cardiac contractility, contributes to diVerences in response pattern between normal and hyperreactors during the cold pressor test. Since the increase in heart rate is mediated by both sympathetic activation and parasympathetic withdrawal and the increase in cardiac contractility is by sympathetic activation, the speciWc response of cardiac function in hyperreactors is likely to be dominated by parasympathetic withdrawal. On the other hand, after the end of immersion, there was no signiWcant diVerence in decreases in heart rate in the two groups of subjects, although the decreases in (dP/dt)/P were larger in hyperreactors than in normal reactors. The decreases in heart rate are mediated by both parasympathetic activation and sympathetic withdrawal through arterial baroreceptor reXex and the decrease in (dP/dt)/P is mainly by sympathetic withdrawal. As a result, the heart rate fully returned to control resting value in both groups of subjects, whereas the (dP/dt)/P did not return to the control resting value in normal reactors. Since the increase in the MBP was largest in the hyperreactors, the strong inhibitory responses of cardiac sympathetic nerves to pressor stimuli in hyperreactors was accompanied by marked vagal activation after the end of immersion (Fritsch et al. 1991; Kollai and Koizumi 1981). Cold sensation, which originates from cutaneous cold receptors, became maximal at around 1 min of cold stress and produces an increase in blood pressure (Wolf and Hardy 1941; Fagius et al. 1989). Pain sensation, which originates from cutaneous nociceptors, modiWes the cold pressor reactions (Fagius et al. 1989; Wolf and Hardy 1941). Peckerman et al. (1991) report that the increase in blood pressure during the cold pressor test depends on the intensity of the perceived pain. Both cold and pain sensations became stronger throughout cold-water immersion in both groups of subjects. However, the pain sensation was strongest in hyperreactors at 60 s during immersion in cold water and could therefore contribute to greater increases in blood pressure. The present study indicates that the cardiac contractility and heart rate increase during cold-water immersion, but not reXect the level of MSNA, and that the responses of cardiac function to cold pressor test in hyperreactors depended on parasympathetic activities rather than on cardiac contractility.

Eur J Appl Physiol (2007) 100:185–191 Acknowledgments We are indebted to Professor emeritus Hisashi Ogawa for his advice and editorial help. We also thank our laboratory students for excellent technical assistance.

References Briggs JF, Oerting H (1993) Vasomotor response of normal and hypertensive individuals to thermal stimulus (cold). Minnesota Med 16:481–486 Cummings MF, Steele PM, Mahar LJM, Frewin DB, Russel WJ (1983) The role of adrenal medullary catecholamine release in the response to a cold pressor test. Cardiovasc Res 17:189– 191 Fagius J, Karhuvaara S, Sundlöf G (1989) The cold pressor test: eVects on sympathetic nerve activity in human muscle and skin nerve fascicles. Acta Physiol Scand 137:325–334 Fritsch JM, Smith ML, Simmons DT, Eckberg DL (1991) DiVerential baroreXex modulation of human vagal and sympathetic activity. Am J Physiol Regutatory Integrative Comp Physiol 260:R635–R641 Green MA, Boltax AJ, Lusting GA, Rogow E (1965) Circulatory dynamics during the cold pressor test. Am J Cardiol 16:54–60 Hejl Z (1957) Changes in cardiac output and peripheral resistance during simple stimuli inXuencing blood pressure. Cardiologia 31:375–381 Hines EA, Brown GE (1936) The cold pressor test for measuring the reactivity of the blood pressure: data concerning 571 normal and hypertensive subjects. Am Heart J 11:1–9 Ifuku H, Taniguchi K, Matsumoto H (1993) Continuous record of carotid artery pulse during exercise. Jpn J Physiol 43:111–116 Ifuku H, Taniguchi K, Matsumoto H (1994) Noninvasive assessment of cardiac contractility by using (dP/dt)/P of carotid artery pulses during exercise. Eur J Appl Physiol 69:244–249 Inoue Y, Miki R, Asami T, Ueda H (2002) Cold-induced vasodilation in prepubertal boys, young and older men. Jpn J Fitt-

191 ness Sports Med 51:291–298 (In Japanese with English abstract) Kasagi F, Akahoshi M, Shimaoka K (1995) Relation between cold pressor test and development of hypertension based on 28-year follow-up. Hypertension 25:71–76 Kollai M, Koizumi K (1981) Cardiovascular reXexes and interrelationships between sympathetic and parasympathetic activity. J Auton Nerv Syst 4:135–148 Kubicek WG, Patterson RP, Witsoe DA (1970) Impedance cardiography as a noninvasive method of monitoring cardiac function and other parameters of the cardiovascular system. Ann N Y Acad Sci 170:724–732 Menkes MS, Matthews KA, Krantz DS, Lundberg U, Mead LA, Qaqish B, Liang KY, Thomas CB, Pearson TA (1989) Cardiovascular reactivity to the cold pressor test as a predictor of hypertension. Hypertension 14:524–530 Morrison SF (2001) DiVerential control of sympathetic outXow. Am J Physiol Regulatory Integrative Comp Physiol 281:R683–R698 Peckerman A, Saab PG, McCabe PM, Skyler JS, Winters RW, Llabre MM, Schneiderman N (1991) Blood pressure reactivity and perception of pain during the forehead cold pressor test. Psychophysiology 28:485–495 Raven PB, Fadel PJ, Ogoh S (2006) Arterial baroreXex resetting during exercise: a current perspective. Exp Physiol 91:37–49 Victor RG, Leimbach WN, Seals DR, Wallin BG, Mark AL (1987) EVects on the cold pressor test on muscle sympathetic nerve activity. Hypertension 9:429–436 Wolf S, Hardy JD (1941) Studies on pain. Observations on pain due to local cooling and on factors involved in the “cold pressor” eVect. J Clin Invest 20:521–533 Wood DL, Sheps SG, Evlebach LR, Schiger A (1984) Cold pressor test as a predictor of hypertension. Hypertension 6:301– 306 Yamamoto K, Iwase S, Mano T (1992) Responses of muscle sympathetic nerve activity and cardiac output to the cold pressor test. Jpn J Physiol 42:239–252

123