| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Polo Tecnologico, Fondazione Don Carlo Gnocchi, ONLUS, Milano, Italy; 2Dipartimento di Medicina Interna, Universita' di Roma "Tor Vergata," and IRCCS San Raffaele Pisana, Roma, Italy; 3IRCCS San Raffaele Pisana, Roma, Italy; 4Centro di Terapia Neurovegetativa, Polo L. Sacco-Universita di Milano, Milano, Italy; 5Department of Clinical Medicine and Prevention, University of Milano-Bicocca, and Department of Cardiology, San Luca Hospital, IRCCS, Istituto Auxologico Italiano Milan, Italy; and 6Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Submitted 9 May 2008 ; accepted in final form 13 August 2008
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
arterial baroreflex; heart rate variability; blood pressure monitoring
Insights in the baroreflex functioning during spaceflights is of importance for the understanding of the complex physiological phenomena and homeostatic imbalance occurring at reentry into a gravitational field (3). Moreover, the mechanisms of adaptation of the baroreflex to microgravity may be of interest also for the astronauts' health during flight. Indeed, due to the disappearance of all gravitational effects, blood pressure is virtually the same everywhere in the systemic arteries throughout day and night. A possible impairment of the baroreflex control during flight might thus theoretically be risky for the astronauts because it may lead to hypertension in cerebral arteries.
Most of the data currently available in this area have been obtained by evaluating baroreflex sensitivity (BRS) in conditions of simulated microgravity obtained through prolonged head-down bed rest (4, 11, 17, 18, 20, 39), in the immediate postspaceflight time (3, 14–16), or under the short-term change in gravity obtained by parabolic flights (25, 36, 37). These studies did not provide univocal results, although the prevalent conclusion was a reduction of BRS after exposure to microgravity.
A direct assessment of baroreflex function during spaceflights was performed in a few studies only (5, 7). However, because of limitations in the schedule of data collection or because of the difficult experimental conditions, no information could be derived on the dynamics of baroreflex cardiovascular control starting from the very beginning of space missions. Indeed, the earliest available evaluation of baroreflex function during a spaceflight was obtained in one subject only, 12 days after launch (5).
In our study, we specifically investigated the features of the adaptation to microgravity of cardiac baroreflex modulation during the 16-day STS 107 Columbia Space Shuttle mission. In particular, we explored the time course of baroreflex adaptation over the whole mission duration, starting from the first day of flight, and collected data both at rest and during physical exercise.
An additional aim of our study was to investigate the possible link between baroreflex function and the action of other neural mechanisms involved in cardiovascular regulation, as quantified by spectral analysis of HR and blood pressure (BP) variability. A further goal was to explore the readaptation of baroreflex cardiac modulation to 1-G gravity after reentry from space. The premature end of the STS 107 mission did not allow this to be accomplished.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Seven studies (including our own) were carried out during the mission, as part of a research program sponsored by the European Space Agency (ESA), and they aimed at investigating cardiorespiratory physiology during spaceflights. This was done by using the Advanced Respiratory Muscular System (ARMS; Damec, Odense, DK), i.e., a multiuser facility measuring ECG, beat-by-beat BP, respiratory movements, and gas composition during respiration of different gas mixtures.
Subjects, Instrumentation, and Protocol
Four astronauts (3 men and 1 woman; age between 42 and 49 yr; body mass index between 23.5 and 27.8 kg/m2) were recruited for the study. The remaining three crew members were responsible for flight operations and were thus unavailable for onboard research activities. All four subjects gave their written consent to the experimental procedures after being informed of their aim and nature. The study was conducted under the guidelines issued by the National Aeronautics and Space Administration (NASA) Johnson Space Center Human Research Policies and Procedure Committee and was also approved by ESA Research and Medical Committees and by the Ethics Committee of the principal investigator's (M. Di Rienzo) Institution.
In each subject, baseline data were collected at the NASA Johnson Space Center, Houston, Texas, four times within a period between 279 and 59 days before the launch. During the spaceflight, data were collected very early after launch, i.e., between hour 8 and 13 (Early 1) and between hour 14 and 29 (Early 2); between day 6 and 8 (Midmission); and between day 12 and 14 (End mission). The timing of the preflight and in-flight experimental sessions and the individual schedules are reported in Table 1. The air pressure onboard was 1atm and the orbital altitude of the shuttle was 307 km.
|
Except for Early 1 (see below), in each experimental session data were recorded in all four astronauts according to the following schedule. First, a 15-min recording was performed while the subjects were sitting on a cycle ergometer without doing any physical activity. In the following 40 min, our recording was stopped, and the astronauts were engaged in mild activities related to other ESA experiments (assessment of O2 and CO2 exchange and evaluation of cardiac output through the rebreathing technique at rest and while pedaling at 50 W). Then the subjects were asked to remain at rest on the cycle ergometer for a period of 3 min to ensure that the baseline condition was restored. During tests performed on the ground before flight, we observed that this time period was sufficient for recovery. Finally a second data recording was performed for 5 min while the subjects were pedaling at 75-W workload. Because of the busy schedule after launch, the first inflight experimental session (Early 1, performed a few hours after launch) was limited to the 15-min recording at rest and was carried out by three astronauts.
Data Analysis
Data acquisition, digitalization (at 12-bit resolution and 100 Hz sampling rate), and storage were carried out by the laptop computer controlling ARMS. During the flight, digitized signals were also downlinked to Earth in real time to allow investigators to monitor the quality of the recordings. This allowed us to rescue most of the inflight data despite the accident that occurred at the end of the mission. The experimental sessions for which data could be recovered are listed in Table 1. Systolic blood pressure (SBP) and-diastolic blood pressure (DBP) were derived from each BP waveform. Left ventricular ejection time (LVET), was estimated as the time interval from the start of the upstroke to the dicrotic notch of each BP wave by the software provided with the Portapres, (Beatscope, version 1.1, FMS, Finapres Medical System, Arnhem, The Netherlands). The beat by beat R-R interval (RRI) was derived from the ECG signal as the interval between consecutive R peaks, after parabolic interpolation of the apex of each R wave (8). For each of the above parameters, mean values and standard deviations were separately estimated during rest and exercise. The root mean square of RRI successive differences (RMSSD) was computed and taken as an indirect index of cardiac vagal modulation (41). Further indirect indexes of autonomic control of circulation were derived from spectral analysis of SBP, DBP, and RRI variability. Each series was resampled evenly at 5 Hz, the Welch periodogram was computed by the fast Fourier transform (FFT), and each spectrum was integrated over the low-frequency (LF; 0.04 to 0.15 Hz) and the high-frequency (HF; 0.15 to 0.50 Hz) region (8, 22, 41). The LF/HF ratio was also computed from the RRI spectrum and taken as an indirect measure of sympathovagal balance in cardiac modulation (30, 41). FFT analysis was also performed on the respiratory signal. The frequency of the highest spectral peak occurring between 0.1 and 0.5 Hz was taken as an estimate of the mean breathing frequency.
Arterial baroreflex. The baroreflex modulation of HR was estimated by the sequence technique (1, 9, 10, 33). Briefly, beat-by-beat SBP and RRI series were scanned in search for sequences of three or more consecutive heartbeats during which 1) SBP progressively increased and, after a lag of zero, one or two beats, RRI progressively lengthened or 2) SBP progressively decreased and, after the same lag, RRI progressively shortened. The slope of the regression line between SBP and RRI values from each sequence was taken as a measure of the sensitivity of baroreflex HR control (BRS). Calculation was also made of the ratio between the number of progressive SBP increases or decreases that were followed by RRI changes (i.e., the number of spontaneous baroreflex sequences as defined above) and the total number of progressive SBP increases or decreases identified over the whole recording period, irrespective of whether they were or were not followed by RRI changes. As reported previously (9), this ratio provides information on how often the baroreflex takes control of the sinus node in response to spontaneous BP changes [baroreflex effectiveness index (BEI)], providing another measure of baroreflex function in addition to BRS.
BRS was also estimated by the alpha coefficient method (31), i.e., the root squared ratio of SBP and RRI spectral powers in either the LF and the HF bands.
Statistical Analysis
To statistically evaluate the results, rest and exercise data obtained in each subject were separately pooled in three different clusters: 1) the "Preflight" cluster included the average of data collected over the four baseline preflight experiments; 2) the "Early 0 G" cluster included data from the first available in-flight experiment; and 3) the "Late 0 G" cluster included the average of data collected at days 6–14 after launch. This clustering strategy allowed obtaining at least one recording for each time slot for each subject.
Differences among the results obtained in the three clusters were assessed by ANOVA for repeated measures, followed by Newman-Keuls post hoc analysis (Statistica 6.0, Statsoft, Tulsa, OK). Estimates of standard deviations, spectral powers, and BRS were log transformed to approximate normal distributions. Statistical significance was assumed for a P < 0.05. Unless differently indicated, data are shown as means ± SE.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
|
Arterial Baroreflex
Figure 2 shows the individual BRS values obtained by the sequence method on ground and during flight. Compared with the preflight condition, BRS measured on the cycloergometer at rest increased strikingly in the early phase of the flight in all subjects. In the two subjects in whom early BRS estimates could be obtained twice (subjects A and D), the first BRS value was greater than the second one. The BRS increase showed a clear-cut attenuation in the mid-late phase of the flight in which BRS tended to return to preflight values. During exercise, BRS was markedly lower than at rest, and it showed no substantial difference between preflight and in-flight values.
|
|
|
At rest, LF and HF RRI powers increased significantly in the early flight phase, with a predominant change in the HF spectral component. Both powers returned to the preflight values in the late flight (Fig. 4, left). The same pattern was observed for the RMSSD of RRI, which increased significantly (P = 0.005) from Preflight (24.8 ± 3.3 ms, mean ± SE) to Early 0 G (37.9 ± 6.9) and returned to preflight values (23.8 ± 2.9) in Late 0 G. The LF/HF power ratio of RRI showed opposite changes, although the trend did not reach statistical significance. The LF powers of both SBP and DBP variability were significantly lower in the Early 0 G compared with Preflight and Late 0 G. The HF powers of SBP, mechanically induced by respiration, were significantly (P = 0.003) higher at Preflight (1.44 ± 0.21 mmHg2) than in Early 0 G (0.88 ± 0.26), displaying a further significant reduction at Late 0 G (0.42 ± 0.08). No significant difference among these three phases was found in all above parameters during exercise (Table 3).
|
|
As shown in Fig. 5, at rest respiratory frequency decreased significantly in the early inflight time and increased again almost to the preflight value in the late flight. As expected, respiratory frequency was greater during exercise than at rest, with no significant differences among experimental sessions.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Indeed, in all four astronauts at rest, BRS displayed a pronounced increase a few hours after launch. Such an increase is suggestive of an enhanced parasympathetic cardiac modulation in the early flight phase. This hypothesis is supported by the concomitant increase in the RMSSD index and in the RRI HF spectral component.
Our study was not aimed at investigating the origin of these modulations. However, in order to shed some light on this finding, we also performed an ancillary analysis of data collected on the ground by one of us (J. M. Karemaker) in the same astronauts in the frame of a different protocol. In this study BP and ECG signals were recorded during supine rest. From these data we estimated BRS by the sequence technique. Results indicate that BRS observed at rest during acute exposure to space microgravity is similar to BRS measured in supine position on earth (18.3 ± 3.4 vs. 21.0 ± 2.8 ms/mmHg; P = 0.60, not significant). These data suggest that the BRS increase occurring during the first hours of exposure to microgravity is mainly caused by the increased pressure at the carotid sinuses due to loss of the hydrostatic component and by centralization of body fluids, and seem to exclude major additional contributions by other factors.
The occurrence of a fluid centralization early in microgravity has been repeatedly observed in the past. Entering microgravity produces a large (1–2 liter) headward fluid shift from the legs (27), results in a stroke volume augmentation of 
46% (44), and causes an increase in the left ventricular end-diastolic dimension (2).
Interestingly, however, it was found that the cardiac filling increase occurring early in microgravity was accompanied by an unexpected decreased central venous pressure (2, 13). It was hypothesized that this might depend either on a rapid increase in diastolic myocardial compliance in space and on an increase in effective filling pressure due to an increase in transmural pressure during spaceflight caused by a more negative extracardial pressure. In this view, it is enigmatic how these mechanical changes occurring inside the rib cage in microgravity might affect the actual stretch of the receptors in the atria and in the large intrathoracic vessels.
Concerning the autonomic response stemming out from the cardiopulmonary receptors, it has been reported that their stimulation, as produced by mechanical or chemical interventions, may produce different reflex effects, leading to either sympathoexcitation (e.g., the Bainbridge reflex) or vagal activation (such as the Bezold-Jarisch reflex), with differences in different animal species. In turn, also the interaction between cardiopulmonary receptors and arterial baroreflex control is not univocal. Indeed, on Earth, BRS usually increases on shifting from upright to supine position, but some authors reported a BRS decrease with volume loading, e.g., in conscious dogs (43) and in humans during lower body positive pressure (38), whereas other groups did not observe any significant BRS change in response to a fluid centralization, e.g., during head-out water immersion (32).
Thus the autonomic response to cardiopulmonary receptors stimulation by blood volume shifts and the interaction between cardiopulmonary and arterial receptors are still unclear issues. Further investigations are required to obtain a coherent interpretative framework for experimental data collected in this field during spaceflights.
However, on the basis of our results and of prior findings of an increase in BRS following a blood centralization in subjects shifting from supine position to a –30° head-down tilt (24), the vagal inhibitory effects seems to prevail in humans in early microgravity condition. Thus it is likely that the central redistribution of blood volume occurring early during a spaceflight would act by stimulating cardiac mechanoreceptors and their prevalent vagal sensory innervation, with ensuing increase in vagal efferent activity and arterial baroreflex sensitivity.
Our results are also compatible with the reported reduction in muscle sympathetic nerve activity observed during acute head-down tilt (6, 40).
In the late flight phase, we observed a reduction toward preflight sitting values in BRS, BP, and HR and in their variability indexes. These changes might be explained by the progressive decrease in blood volume, which has been shown to occur during a prolonged exposure to microgravity (21), with the related readjustment of the cardiovascular control mechanisms. However, it cannot be excluded that these changes might depend also on a deconditioning of the autonomic control of the heart occurring over time.
A direct answer to such a question would have been provided by the scheduled postflight experiments, not performed for the premature end of the mission. However, data collected during exercise do not seem to support this hypothesis. Indeed, when the astronauts were engaged in physical exercise, the BRS values observed both before and during the spaceflight were similar. This supports the conclusion that the ability of the cardiac baroreflex to respond to mild physiological challenges, like the 75-W exercise, is preserved during microgravity exposure, and it does not favor the hypothesis of a deconditioning.
It should be noticed, however, that when the cardiovascular system has to face more strenuous activity in space, other biological mechanisms are likely to intervene and somewhat limit the intrinsic effectiveness of the baroreflex in controlling the heart. Indeed, in a different experiment performed on the same four astronauts at days 12 and 13 of the STS-107 mission, our group observed that metaboreflex mechanisms are enhanced during heavy dynamic exercise in space, and this potentiation negatively interferes with the vagally mediated baroreflex control of HR (19).
The baroreflex function at reentry was explored by several studies in the past, and most of them observed a reduction in BRS right after landing. On the basis of our results, we can speculate that the observed impairment of cardiac baroreflex sensitivity at reentry from a space mission, rather then being the direct result of a progressive deconditioning of the baroreflex function during spaceflight, might depend on an adverse interference with the baroreflex exerted by other mechanisms acutely triggered by return to the earth gravitational field. Among them is the sympathetic activation elicited by reexposure to the gravity field (20, 23, 29, 42) in the presence of flight-induced reduction in plasma volume (21).
Limitations
We acknowledge three limitations of our study. First, data could be collected during the flight from four subjects only. A small sample size is a common characteristic of studies carried out during spaceflights. This inherent limitation, however, was recognized not to prevent relevant observations to be obtained (19, 35), and, in our case, it was compensated by the strength of our observations. Indeed, we found similar BRS trends in all four subjects, independently from the sex, during spaceflight, and this led to statistically significant results. However, the low number of subjects might have prevented the identification of significant changes in other variables (type II error).
Second, our study was planned to specifically explore the baroreflex adaptation over a 16-day space mission. Thus, we cannot exclude that further changes might have occurred in case of a longer exposure to microgravity.
Third, arterial BP was recorded on a beat-by-beat basis by making use of Portapres, as commonly done in space experiments. It should be recalled that the accuracy of this device is adequate for the measurement of BP variability and for the assessment of baroreflex function (32, 28), but it may be somewhat limited in the assessment of BP absolute values. For this reason, in the original protocol of our study we asked for a manual BP measurement by the traditional Riva-Rocci cuff before each experiment, so to calibrate the absolute values of the Portapres. Unfortunately, these measurements could not be included in the final schedule and thus calibration was not possible.
Conclusions
HR baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart.
|
GRANTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
Research of J. M. Karemaker was supported by the Space Research Organization Netherlands.
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
The authors are also grateful to Dr. Giovanna Branzi for her valuable contribution and expertise during data collection.
|
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  M Di Rienzo, G Parati, A Radaelli, and P Castiglioni Baroreflex contribution to blood pressure and heart rate oscillations: time scales, time-variant characteristics and nonlinearities Phil Trans R Soc A, April 13, 2009; 367(1892): 1301 - 1318. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
) and during 75-W exercise (
), estimated during the flight and plotted vs. the mission elapsed time (ET), namely the time from launch expressed in days. For comparison, BRS values before flight (Pre) are also shown as means and SE.
