Noninvasive Evaluation of Cardiac Output during Postural Change and Exercise in Humans: Comparison between the Modelflow and Pulse Dye-Densitometry

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1 Japanese Journal of Physiology, 54, , 2004 Noninvasive Evaluation of Cardiac Output during Postural Change and Exercise in Humans: Comparison between the Modelflow and Pulse Dye-Densitometry K. MATSUKAWA, T. KOBAYASHI*, T. NAKAMOTO, J. MURATA, H. KOMINE, and M. NOSO* Department of Physiology and * Department of Health Science, Graduate School of Health Sciences, Hiroshima University, Hiroshima, Japan Abstract: To investigate whether the Modelflow method, by simulating the aortic input impedance model from a noninvasive monitoring of arterial blood pressure, reflected a reliable measure of cardiac output (CO) during postural change and whole-body exercise occurring in daily life, we compared the Modelflow-estimated CO with a simultaneous reference determined by the pulse dye-densitometry. Nine healthy volunteers performed postural change from supine to upright and dynamic stepping exercise. The Modelflow-estimated CO decreased to l/min, from l/min, during the postural change and increased to l/min during a stepping exercise, returning to l/min at 5 min after exercise. When comparing the pooled data of CO during resting and following exercise between the Modelflow and pulse dye-densitometry, we found that the average CO did not differ between the two estimates and that there was a significant correlation between them; the slope of the linear regression line corresponded to approximately 1.0. Although such linear relationship was also observed in an individual subject, the slope of the regression line varied from to among the subjects. The calibration of the Modelflow-estimated CO with the dye-densitometry value at supine or upright improved a correlation between the two estimates. Thus it is likely that the noninvasive Modelflow simulation from arterial blood pressure can provide a reliable estimation of group-average cardiac output during postural change and stepping exercise occurring in daily life. It will be recommended for a more accurate estimation of cardiac output in a given subject to calibrate the Modelflow data with an independent measure. [The Japanese Journal of Physiology 54: , 2004] Key words: beat-to-beat measurements, arterial blood pressure, stroke volume, dynamic exercise, upright posture. Noninvasive and continuous measurement of cardiac output (CO) is essentially important for a better understanding of the cardiovascular adaptation to postural changes and whole-body exercise naturally occurring in daily life. Wesseling et al. [1] have developed a new method to compute aortic blood flow from arterial pressure wave by simulating a nonlinear, timevarying three-element model of aortic input impedance, termed the Modelflow method. Integrating the computed aortic flow waveform per beat provides stroke volume (SV), and the beat-to-beat value of CO is calculated by multiplying SV and instantaneous heart rate. When CO estimated by the Modelflow from an arterial pressure signal was compared with that obtained from the standard thermodilution technique during cardiac surgery, there was a significant correlation between them, and the pooled mean difference was 6 7% [1, 2]. Furthermore, the Modelflowestimated CO matched that determined by thermodilution or by Doppler ultrasound during orthostatic stress in healthy subjects [3, 4]. Taken together, the three-element model simulation of aortic blood flow Received on December 30, 2003; accepted on March 12, 2004 Correspondence should be addressed to: Kanji Matsukawa, Department of Physiology, Graduate School of Health Sciences, Hiroshima University, Kasumi 1 2 3, Minami-ku, Hiroshima, Japan. Tel: , Fax: , matsuk@hiroshima-u.ac.jp Japanese Journal of Physiology Vol. 54, No. 2,

2 K. MATSUKAWA et al. from arterial pressure wave appeared useful for monitoring the beat-to-beat changes in CO and SV at rest and under orthostatic stress. However, it remained little known whether the Modelflow method could be applied during voluntary postural changes and exercise occurring in daily life. Recently the Modelflow-estimated CO has been tested during bicycle ergometer or treadmill exercise in comparison with CO independently determined by CO 2 - or acetylene-rebreathing [5 7] or by Doppler ultrasound [8]. The studies showed that the Modelflowestimated CO during exercise linearly correlated to that obtained from another method. However, there was a sizable difference between the two estimates, though it was not statistically significant. The greater an intensity of ergometer exercise raised to 60% of the maximal capacity or 130% of the ventilatory threshold, the more the Modelflow tended to underestimate CO by 2.8 l/min than that by CO 2 -rebreathing [5] or to overestimate it by 2.4 l/min than that by Doppler ultrasound [8]. Furthermore, it tended to overestimate CO by 1.8 l/min near the maximal capacity of ergometer exercise [6] and by 2.4 l/min during maximal treadmill exercise [7] in comparison with CO 2 -rebreathing or acetylene-rebreathing. Because of such deviation, it was questioned that the Modelflow monitoring of CO and SV from the arterial pressure signal might be accurate enough to estimate those parameters during exercise by a given subject [5, 8]. To further investigate whether the noninvasive Modelflow method was a reliable measure of CO during physical activity naturally occurring in daily life, we compared the Modelflow-estimated CO with that derived from the pulse dye-densitometry as a reference measure. Nine healthy volunteers performed postural change from the supine to the upright posture and dynamic exercise in the upright posture (stepping on stairs). It is known that a difference in CO between the dye-densitometry and thermodilution during cardiac surgery is small ( l/min) [9 11]. Also, we identified the beat-to-beat changes in CO and SV by using the Modelflow method; the changes were expected to decrease in the upright posture and to increase during the dynamic stepping exercise. METHODS Subjects. Eight males and one female participated in this study. The experimental protocols were approved by the Institutional Ethical Committee and were well explained to them. A written informed consent was obtained from all subjects. The age of the subjects was years; body weight kg, and height cm. They were healthy and none had taken any medication. Measurements. A pair of electrodes (Magnerode TE-18M-3, Fukuda Denshi, Tokyo, Japan) was attached to the chest for an electrocardiogram (ECG) recording. The ECG signal and respiratory movement were simultaneously monitored by a telemeter system (Dynascope DS-3140, Fukuda Denshi, Tokyo, Japan). A venous catheter was inserted into the left antecubital vein for dye injection and blood withdrawal. A blood pressure cuff was attached to the middle or index finger of the right hand to perform noninvasive and continuous monitoring of arterial blood pressure (AP) with a Finometer (Finapres Medical Systems BV, Arnhem, Netherlands) [12]. A conventional pressure cuff was wrapped around the same upper arm as the finger cuff. A brachial artery blood pressure wave was reconstructed from the finger blood pressure by conducting a return-to-flow calibration with an inflation of the upper arm cuff. The Finometer system was also equipped with a height correction system for the position of the finger blood pressure cuff, allowing the subtraction of the hydrostatic pressure difference between levels of the heart and the finger cuff. A pulse dye-densitometry probe, which consisted of lightemitting diodes and photo sensors, was attached at the nose to calculate a dye dilution curve of indocyanine green (ICG; Diagnogreen, Daiichi Pharmaceutical, Tokyo, Japan) administered intravenously [9]. Experimental protocols. It is important for a basic physiological understanding and for clinical health care to clarify the cardiovascular adaptation during dynamic exercise naturally occurring in daily life (such as using stairs, walking, and jogging), which is mostly performed in the upright posture with largemuscle mass activity. Following this idea, in the present study we chose an exercise on stairs with the upright posture. After all preparations of the catheter and instruments were completed, each subject lay in a supine position and for more than min was allowed to stabilize the cardiovascular variables. Each one thereafter stood up and remained quiet in the upright posture for 5 min, then performed dynamic exercise for 10 min, stepping upward and downward on stairs at an arbitral rhythm. Following the cessation of the dynamic exercise, each subject quietly kept the upright posture at least for 5 min. To measure cardiac output by using the pulse dye-densitometry, we conducteded an intravenous injection of ICG (5 mg) dissolved in saline of 1 ml four to six times throughout the experiment (at rest in the supine and upright postures and immediately and 5 min after the stepping exercise ended). An individual ICG administration was 154 Japanese Journal of Physiology Vol. 54, No. 2, 2004

3 Noninvasive Cardiac Output in Humans flushed with a bolus injection of 20 ml heparinized saline. The time interval of 4 5 min between ICG injections was long enough for a plasma concentration of ICG to become negligible. Modelflow. Arterial blood pressure waveform was sampled at a frequency of 200 Hz. The beat-tobeat values of systolic (SAP), mean (MAP), and diastolic arterial blood pressure (DAP) and heart rate (HR) were measured. The beat-to-beat values of stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were simultaneously calculated with Modelflow software (BeatScope 1.1, Finapres Medical Systems BV, Arnhem, Netherlands). The Modelflow method used a nonlinear three-element model of the aortic input impedance to compute an aortic flow waveform from the arterial pressure wave, as reported in detail [1 3]. The three elements corresponded to the characteristic impedance of the aorta (Z 0 ), the total arterial compliance (C w ), and a peripheral vascular resistance (R p ). Z 0 was connected in series to a parallel circuit of C w and R p. Z 0 and C w were dependent on the elastic properties of the aorta and varied in a nonlinear manner with distending pressure. R p was defined as the ratio of mean arterial blood pressure to mean aortic flow. After the instantaneous values of Z 0 and C w were obtained from a builtin database of arctangent area pressure relationships given subject gender and age as input, these values were used in the model simulation for computing an aortic flow waveform. R p was calculated for each beat by the model simulation and updated. The Modelflow method thus computed stroke volume from the arterial pressure wave, with continuous nonlinear corrections for variations in aortic diameter, compliance, and impedance during the arterial pulsation. Integrating the aortic flow waveform per beat provided left ventricular stroke volume. Dye-densitometry. To calculate CO from the change in ICG concentration in the peripheral arterial blood, we used the ratios of ICG concentration to hemoglobin concentration at the two light-wave lengths of 805 and 940 nm; the extinction coefficient of ICG in blood was at the maximum at 805 nm and was nearly zero at 940 nm. Furthermore, the difference in the oxyhemoglobin and deoxyhemoglobin absorbance at the wave length of 805 nm was so small that the ICG concentration in blood could be photometrically calculated from the ratio of ICG concentration to total hemoglobin concentration for each pulse by using the hemoglobin value measured by other means. A dye dilution curve of the first pass of ICG through the nasal photosensors was obtained with a pulse dye-densitometry analyzer (DDG-2001, Nihon Kohden, Tokyo, Japan). Venous blood (volume, 3 ml) was sampled at rest in the supine condition and 5 min after the end of exercise to detect the absolute content of hemoglobin in the blood. We examined the relationship between the simultaneous data of CO obtained by the Modelflow method from a noninvasive arterial blood pressure signal and by the dye dilution method. Statistical analysis. The cardiovascular parameters estimated from the noninvasive measurement of AP with the Finometer and CO from the dye-densitometry observed before, during, and after a dynamic stepping exercise were statistically analyzed by a one-way analysis of variance (ANOVA) with repeated measures and a Tukey post hoc test. In particular, we analyzed the pooled data of CO by using a two-way ANOVA with repeated measures having two main effects: (1) the four different conditions (supine rest, upright rest, and immediately and 5 min after exercise) and (2) the two methods (Modelflow and dyedensitometry). The relationship in CO between the Modelflow and the pulse dye-densitometry was examined by a linear regression analysis. The level of the statistical significance was p All data are indicated as means SEM. RESULTS Beat-to-beat cardiovascular changes from noninvasive arterial blood pressure during postural change and during dynamic exercise The time courses of the beat-to-beat changes of HR, SV, CO, MAP, and TPR throughout the experiment are exemplified in Fig. 1. The average cardiovascular responses during postural change and during dynamic exercise are summarized in Table 1. When the posture was shifted to upright from supine, SV decreased to ml, from ml. CO transiently increased and then tended to decrease, but TPR altered in the opposite direction; the decrease in CO was not significant because of a compensatory rise in HR; TPR increased to medical units (MU mmhg/ml/s), from MU. As soon as the stepping exercise was started, SV and HR rapidly increased, indicating a quite large increase in CO. TPR was abruptly decreased at the start of the exercise. During the later period of exercise, HR continued to increase to beats/min until the exercise ended, contributing to a further rise in CO to l/min during that period. SV remained elevated at ml, but showed no further increase. MAP continued to elevate to mmhg, and TPR continued to reduce to MU until the exercise ended. After the cessation of the stepping ex- Japanese Journal of Physiology Vol. 54, No. 2,

4 K. MATSUKAWA et al. Fig. 1. The time courses of the beat-to-beat changes in heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial blood pressure (MAP), and total peripheral resistance (TPR) throughout the experiment in one subject. After lying in the supine position, the subject stood up and remained quietly in the upright posture for 5min and then performed dynamic whole body exercise for 10 min, stepping upward and downward on stairs at an arbitral rhythm. Following the cessation of the dynamic exercise, the upright posture was kept for 5 min. All traces show the beat-to-beat cardiovascular changes obtained by use of the Finometer and the Modelflow method. A dye of indocyanine green (ICG, 5 mg) was I.V. injected five times throughout the experiment, as indicated by arrows ( ), to simultaneously measure cardiac output by the use of pulse dye-densitometry. ercise, all cardiovascular parameters except MAP recovered gradually to the control levels in the upright posture with a long delay of 3 5 min; MAP returned to a level near control as soon as the dynamic exercise ended. Comparison between the cardiac output data from the arterial blood pressure wave and the dye-densitometry The relationships between the cardiac output data obtained by use of the two different methods (Modelflow and pulse dye-densitometry) in two subjects and in all nine subjects, respectively, are shown in Fig. 2. In the pooled data, a significant correlation between them was found, and the linear regression line was Y 0.978X [correlation coefficient (g) 0.626, p ]. As shown in Fig. 2A, this linear relationship between the cardiac output data was also observed in an individual subject, but the slope of the regression line ranged from to among the subjects. This implied that if the original data of the Modelflow-estimated CO were recalculated with a calibration factor derived from a ratio of the two estimates of CO at rest in the supine or upright posture, the calibrated data might improve the relationship and provide a more accurate estimation of the cardiac output in a given subject. Figure 3 illustrates the relationship in CO between the calibrated Modelflow and dye-densitometry. The calibration clearly improved a correlation between them, but the slope of the regression lines became slightly steeper; the correlation coefficient (g) increased to The original noncalibrated data of CO obtained in each of the four conditions (at rest in the supine posture, at rest in the upright posture, and immediately and 5 min after stepping exercise) are compared between the two different methods (Modelflow and pulse dye-densitometry) in Table 1. Using the noncalibrated and calibrated data of CO, we plotted the average differences between the two estimates against the grand means of CO in Fig. 4. Indeed, there were no significant differences between the two in each of the four conditions, but the noncalibrated Modelflow CO tended to be greater by l/min during resting than that determined by the dye-densitometry. It tended to be smaller, however, by l/min after the stepping exercise (Fig. 4A). Similarly, the calibrated Modelflow tended to underestimate CO by l/min following the stepping exercise (Fig. 4B and C), compared with the dye-densitometry. DISCUSSION Noninvasive and continuous measurement of CO is essentially needed to clarify the cardiovascular adaptation to postural changes and whole-body exercise occurring in daily life. Wesseling et al. [1] has developed the Modelflow method to compute aortic blood flow from arterial pressure wave by simulating a nonlinear, time-varying three-element model of aortic input impedance. To investigate whether the noninvasive Modelflow method reflected a reliable measure of CO during postural change from supine to upright and during dynamic stepping exercise on stairs, we compared the Modelflow-estimated CO with the simultaneous reference determined by the pulse dye-densito- 156 Japanese Journal of Physiology Vol. 54, No. 2, 2004

5 Noninvasive Cardiac Output in Humans Table 1. Comparison of average cardiac output obtained from the Modelflow-calculation method from arterial blood pressure and by the pulse dye-densitometry methods in the same subjects (n 9). Resting Resting During exercise Immediately after 5 min after (supine) (upright) (upright) exercise (upright) exercise (upright) A. Cardiovascular data obtained from arterial blood pressure signal with the Modelflow method SAP (mmhg) *, * MAP (mmhg) *, * DAP (mmhg) * *, * * HR (beats/min) *, *, *, SV (ml) * * CO (l/min) *, TPR (MU) * *, B. Cardiac output data obtained from pulse dye-densitometry CO (l/min) *, Hb (g/dl) * Ht (%) SAP, systolic arterial blood pressure; MAP, mean arterial blood pressure; DAP, diastolic arterial blood pressure; CO, cardiac output; HR, heart rate; SV, stroke volume; TPR, total peripheral resistance; MU, medical unit ( mmhg/ml/s); Hb, hemoglobin concentration in blood; Ht, hematocrit. Because venous blood was not withdrawn during resting (upright) and immediately after the end of exercise, Hb and Ht were not determined in the periods. * Significant changes from the control data during resting (supine). Significant changes from the control data during resting (upright). metry. There was a significant correlation between the two estimates in the CO data pooled during resting and following exercise, and the slope of the linear regression line corresponded to approximately 1.0. Furthermore, when comparing the CO data in each of the four conditions (at rest in supine posture, at rest in upright posture, and immediately and 5 min after stepping exercise), we found no significant changes in the average CO between the two estimates. Taken together, it is quite likely that the two independent procedures gave the matched values of cardiac output on average, and that the noninvasive Modelflow simulation from arterial blood pressure can provide a reliable estimation of group-average cardiac output during postural change and stepping exercise. Whether the Modelflow method reflects a reliable noninvasive measure of cardiac output during exercise has so far been controversial. The Modelflow-estimated CO was tested during ergometer or treadmill exercise in comparison with CO independently determined by CO 2 - or acetylene-rebreathing [5 7] or by Doppler ultrasound [8]. These studies reported that there was a significant correlation between the two estimates, but the Modelflow tended to underestimate CO [5] or to overestimate [6 8]. Most studies regarded the Modelflow method as a reliable method within the limits of its use (i.e., to use only group-average data to be examined and to calibrate only with an invasive method) [6 8]; however, one study considered it unreliable [5]. Our present study using the simultaneous comparison between the Modelflow and dye-densitometry supported the view that as far as the group-average value of CO is concerned, the Modelflow method can supply useful information about the beat-to-beat changes in CO. Furthermore, we noted that there was a linear relationship between the two estimates in an individual subject, but the slope of the regression line varied among subjects. After the original data of the Modelflow-estimated CO was calibrated with a factor defined as a ratio of the Modelflow and dye-densitometry estimates of CO at rest in the supine or upright posture, the calibrated data showed an improved correlation between the two estimates. Thus for a more accurate estimation of cardiac output in a given subject, it is recommended that the Modelflow data be calibrated with an independent measure, as previously suggested [2, 7, 13, 14]. Even though the calibration was conducted, we observed a difference between the two estimates following exercise (Fig. 4). Although it remains unanswered whether the difference is due to an underestimation by the Modelflow or an overestimation by the dye-densitometry, several limitations responsible for the difference are considered. First, the most serious one with respect to the Modelflow may be the reliability of the parameters for the three-element model of the aortic input impedance. The absolute values and their pressure-dependent characteristics of the model parameters have been estimated by use of the pressure lumen area relationship of in vitro human thoracic and abdominal aortas [15]. Such estimated parameters of the aortic input impedance model, however, do not always Japanese Journal of Physiology Vol. 54, No. 2,

6 K. MATSUKAWA et al. Fig. 2. The relationships between the noncalibrated data of cardiac output obtained by the two different methods (Modelflow vs. pulse dye-densitometry). A: Correlations between the cardiac output data obtained by the Modelflow and pulse dye-densitometry methods in two subjects. B: Correlation between the noncalibrated data of cardiac output obtained by the Modelflow and pulse dyedensitometry methods in all nine subjects. In each panel, the linear regression line ( ) and 95% prediction interrupted lines ( ) between the cardiac output data are plotted, and its equation and correlation coefficient (g) are inserted. There was a significant correlation between them, and the slope of the regression line was 0.978, suggesting that the two different methods give corresponding values of cardiac output on average. fit an individual human, and this may result in a variation in the relationship in CO between the Modelflow and dye-densitometry. Second, the waveform of the noninvasive arterial blood pressure does not strictly equal that of aortic blood pressure, which may affect the simulation of a nonlinear, time-varying three-element model of aortic input impedance and cause another error in computing aortic blood flow. Third, since a good photosensor signal could not be obtained during exercise because of movement artifact, we had to measure the CO by the dye-densitometry at the transient phase following exercise. An error in the sampling period might be involved, but a manually marking signal was used to synchronize the Finometer and dye-densitometry signals. Fourth, venous blood was not withdrawn during the upright rest nor immediately after exercise. Because the hemoglobin concentration in the supine rest and 5 min after exercise was substituted for them, this substitution may induce another error in the CO determined by the dye-densitometry. These limitations can explain at least partly the difference in the CO relationship between the Modelflow and dye-densitometry. The measurement of CO and SV during postural change and physical activity (such as stepping on stairs, walking, and jogging, which are mostly performed with a large muscle mass in the upright posture), was a difficult task. Although it is important for basic physiological understanding and clinical health care to identify the cardiac responses, the reliable data of CO and SV in the unrestrained state was lacking. We have measured for the first time the cardiac responses to postural change and stepping exercise in a freely moving condition, because the Modelflow is considered to provide a reliable estimation of groupaverage CO, as mentioned above. The cardiac responses during postural change from supine to upright are very interesting. A large decrease in SV caused a slight reduction in CO during the upright posture because of a compensatory increase in HR. Decreased venous return during standing may reduce cardiac filling, resulting in a reduction in SV. On the other hand, MAP was well maintained by a rise in TPR, indicating systemic vasoconstriction. The fundamental characteristics of the cardiovascular responses were in agreement with those of the cardiovascular responses that were recorded by the use of thermodilution or by Doppler ultrasound during passive head-up tilting [3, 16]. This similarity suggests two things. One is that a feedback reflex mechanism from cardiopulmonary baroreceptors may play a role in the cardiovascular adjustment during both active standing and passive head-up tilting. The other is that the beat-to-beat data obtained by the Modelflow corresponds to those measured by the Doppler ultrasound, suggesting a validity of the Modelflow as a noninvasive monitoring of CO and SV. The beat-to-beat cardiac responses during voluntary stepping exercise with the upright posture are also quite impressive. The dynamic responses were qualitatively divided into the initial and later responses (Fig. 1). At the start of the stepping exercise, HR and SV both increased abruptly, evoking a large increase of CO. The abrupt responses suggest that a feedfoward control by central command from the higher 158 Japanese Journal of Physiology Vol. 54, No. 2, 2004

7 Noninvasive Cardiac Output in Humans Fig. 3. The relationships between the calibrated data of cardiac output obtained by the two different methods (Modelflow vs. pulse dye-densitometry). The original noncalibrated data of the Modelflow-estimated CO were calibrated with a factor defined as a ratio of the Modelflow and dyedensitometry estimates at rest in the supine (A) or upright posture (B). The calibration clearly improved a correlation between them, but the slope of the regression lines became slightly steeper; the correlation coefficient (g) increased to In each panel, the linear regression line ( ) and 95% prediction dotted lines ( ) for the calibrated cardiac output data are plotted, and its equation and correlation coefficient (g) are inserted. Also, these lines for the noncalibrated cardiac output shown in Fig. 2B are superimposed. Fig. 4. Differences between the cardiac output data determined by the pulse dye-densitometry and the Modelflow method [ CO Dye CO Modelflow ] are plotted against the grand mean values of cardiac output [ (CO Dye CO Modelflow )/2] in the four conditions (at rest in supine posture [a], at rest in the upright posture [b], and immediately [c] and 5 min [d] after the end of dynamic exercise. A: For the noncalibrated cardiac output data. B: For the calibrated cardiac output data with a factor defined as a ratio of the Modelflow and dye-densitometry estimates at rest in the supine posture. C: For the calibrated cardiac output data with a factor defined as a ratio of the Modelflow and dye-densitometry estimates at rest in the upright posture. brain centers contributes to the rapid cardiac adaptation at the start of exercise. On the other hand, HR and CO gradually increased during the later period until the exercise ended, but SV remained constant at that period (Fig. 1). The tachycardia, therefore, plays a more important role in elevating CO in the later period of exercise. As one of the neural mechanisms responsible for the later cardiac adaptation, the exercise pressor reflex is considered [17]. If mechanoreceptors and metaboreceptors in the contracting muscles are activated during exercise, it is known that stimulation of the muscle receptors initiates a reflex increase in HR via cardiac sympathetic efferent nerve activity [18]. Assuming that the exercise pressor reflex contributes to the cardiac adaptation during the later period of exercise, the reflex may influence cardiac sinus rhythm instead of left ventricular contractility. In conclusion, we have revealed that the Modelflow and pulse dye-densitometry method gave the matching average values of cardiac output during postural changes and following dynamic stepping exercise naturally occurring in daily life. It is most likely that the noninvasive monitoring of cardiac output by the Modelflow provides a reliable estimation of cardiac output at least as far as the group-average value of cardiac output is concerned. This study was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by a grant from Ground-based Research Announcement for Space Utilization promoted by Japan Space Forum. We appreciate Nihon Kohden Corporation for allowing us to use the pulse Japanese Journal of Physiology Vol. 54, No. 2,

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