Acta Astrona,tica Vo1.24, pp. 323-328, 1991 Printed in Great Britain
0094-5765/91 $3.00 + 0.00 Pergamon Press pie
CARDIOVASCULAR FUNCTION IN SPACE FLIGHT A. E. Nicgossian, J. B. Charles, M. W. Bungo and C. S. Leach-Huntoon National Aeronautics and Space Administration Washington, D.C. Abstract Changes in orthostatic heart rate have been several days thereafter. It is hypothesized noted universally in Soviet and U.S. that the early adaptation to space flight crewmembers post space flight. The magni- involves a central fluid shift during the initial tude of these changes appears to be infludays of flight, but subsequent alterations in enced by mission duration, with increasing neural controlling mechanisms (such as orthostatic intolerance for the first 7-10 days carotid baroreceptor function) contribute to of flight and then a partial recovery in the orthostatic intolerance. orthostatic heart rate response. Fluid loading has been used as a countermeasure to Introduction this post/light orthostatic intolerance. Previous reports have documented the effectivePostflight orthostatic intolerance was one of ness of this technique, but it has also been the earliest and most consistent findings noted that the effectiveness of volume associated with manned space flight (1). expansion diminishes as flight duration This prompted an extensive ground and exceeds one week. The response of carotid flight investigation program to understand baroreceptor function was investigated the mechanisms, time-course of adaptation, utilizing a commercially available neck collar and the development of countermeasures which could apply positive and negative (1,2,3,4). Metabolic and endocrine changes pressure to effect receptor stimulation. have been carefully investigated to correlate Bedrest studies had validated the usefultheir regulatory effect on the overall cardioness and validity of the device. In these vascular function (5,6,7). More recently, studies it was shown that carotid barorecep- attempts have been made to understand the tor function curves demonstrated less rerole of neural control in the overall responsiveness to orthostatic stimulation than sponses of cardiovascular systems. The control individuals. Twelve Space Shuttle purpose of this paper is to review the results crewmembers were examined pre- and of these investigations. post/light from flights lasting from 4-5 days. Plots of baroreceptor function were conMethods structed and plotted as change in R-R interval vs. carotid distending pressure (an Experiments were conducted on the seven orthostatic stimulus). Typical sigmoidal STS missions since STS-26. These investicurves were obtained. Post/light the resting gations consisted of orthostatic tolerance, heart rate was higher (smaller R-R interval) cardiac hemodynamics D using ultrasound and the range of R-R value and the slope of scanning, and baroreflex function m using a the carotid sigmoidal response were both neck pressure device (8). depressed. These changes were not significant immediately post/light (L+O), but did Stand tests were performed on all space become significant by the second day postflight crews, preflight, immediately posfflight, flight (L+2), and remained suppressed for and 3-7 days postflight. This technique
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consists of the crewmember being in a supine position for 5 minutes and then subsequently in a passive standing position with his/her feet placed approximately 6 to 9 inches from the wall and with the back leaning slightly against the wall. Heart rate is monitored continuously by ECG and blood pressure is taken every minute manually by sphygmomanometry. This technique is identical to that used for all U.S. Shuttle missions to date and has been described in detail in previous publications. During this stand test procedure, ultrasound examination of the heart is performed utilizing two-dimensional, M mode, and limited doppler echocardiography. Echocardiographic scans are performed at a minimum in the parasternal long axis, parasternal short axis, and four-chamber apical views. Other views or variations are performed as needed to improve image quality. Measurements and calculations are made of left ventricular diastolic and systolic volume, stroke volume, fractional shortening, ejection fraction, cardiac output, cardiac wall dimensions, left atrial size, aortic size, right ventricular size, velocity of circumferential fiber shortening, left ventricular mass, left ventricular stroke work, and total peripheral resistance. These techniques are wellstandardized in clinical and research practices in the United States and also are identical to the techniques employed in our previous investigations. A doppler examination of aortic flow was added to the routine ultrasound examinations. A pulsed doppler signal is directed at the left ventricular outflow from the apical view. The velocity profile from this sampling is used with the outflow tract dimension taken from the parasternal long axis view and coupled with the heart rate from electrocardiographic monitoring to calculate minute-by-minute cardiac output.
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In an effort to supplement the hemodynamic measurements obtained with the above techniques, carotid baroreflex stimulation to delineate changes in the neurohumoral responses of the cardiovascular system was added. Both preflight and at selected intervals postflight, carotid baroreceptor reflex control of the sino-atrial node is investigated by use of a neck pressure chamber. Each study was performed with the subject in a resting supine posture for 20 minutes, during which time the subject is instrumented with a respiratory indicator, a lead II electrocardiogram, a Finapres finger blood pressure monitor, and the neck chamber device. The subject breathes ambient air quietly for a minimum of 5 minutes during this rest period while respiration, ECG, and blood pressures are recorded. The subject remains supine and at the end of held expiration, 40 mmHg of pressure is applied through the neck collar and after approximately 5 seconds the pressure is stepped down in R wave triggered 15 mm intervals to -65 mm of mercury, after which the neck pressure returns to ambient level. For each subject, the stimulus train is delivered seven times and neck pressures and R-R intervals are averaged. Neck chamber pressures are subtracted from systolic pressures to derive estimates of carotid distention pressures
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and these are plotted against corresponding R-R intervals. Results and Discussion Orthostatic intolerance has been manifested postflight by 30-50 percent of the astronauts that have flown. This has been manifested by increased heart rates and decreased blood pressures and in clinically symptomatic individuals as episodes of syncope or near syncope. Figure 1 demonstrates data from U.S. manned space flights from 19621985 which clearly show an increase in the
of cardiovascular adaptation. Unfortunately, the data available from longer space flights is not sufficient in number to comment upon possible mechanisms for these phenomena. FIGURE 2 SHUTTLE DATA (4-5 DAY FLIGHTS) I
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orthostatic heart rate; that is, the change in heart rate in the standing position postflight compared to that preflight. Despite the variation in mission durations, it appeared that orthostatic intolerance was a consistent finding. However, several interesting phenomena were noted. Firstly, there appeared to be improvement in orthostatic function with use of a fluid loading countermeasure. These results will not be discussed further in this paper as they have been published previously (4). Secondly, it was also noted that whether a countermeasure was used or not used, there appeared to be a second phase of orthostatic adaptation occurring some time after the 8th day of space flight. In addition, there may be a later third phase
Figure 2 shows the results of carotid baroreflex examination performed on U.S. Shuttle crewmembers during the latter half of 1988 and the first 10 months of 1989. Ten subjects had their baroreflex function examined, and it is noted from this figure that heart rate postflight is elevated over preflight. This finding is consistent with all known previous space flight data. However, it is also noted that the range of the R-R interval or the slope of the baroreflex curve is not altered during this time period. One must interpret this data in relation to the bedrest data presented earlier and reference is once again made to Figure 5, which showed that after 3 days of bedrest the baroreflex did not change significantly in spite of the fact that continued bedrest did produce alterations. It may be that space flight duration was merely not long enough to effect changes in these crewmembers. Figure 3 illustrates one of the sequential curves obtained on a crewmember from this sample. It shows that although baroreflex
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function on L+O, which is immediately postflight, had not changed remarkably from preflight, subsequent examinations during the recovery period did show change in both slope and R-R range. In fact, when data from 12 astronauts is pooled as demonstrated in Figure 4, we see that at landing plus 2 days there is a change in baroreflex function which is significant to the P
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Figure 5 illustrates the changes in stroke index during the orthostatic stress of standing both pre- and postflight. It is interesting to note that these curves are quite similar, so that it appears stroke volume remains preserved after short flights. It must be noted that all crewmembers participating in this examination had consumed approximately a liter of fluid and eight one-gram salt tablets prior to Shuttle landing. This fluid loading countermeasure, we believe, assisted in preserving hemodynamic stroke index stability. Figure 6 shows the heart rates expressed as the R-R interval. It is once again evident that heart rate is elevated postflight, both in the supine and the standing positions, and that the magnitude of elevation with orthostatic stress is greater postflight than it was FIGURE6 PASSNESTANDTESTSHUTTLEDATA
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preflight. This elevated heart rate response, when coupled with a fairly stable stroke volume response, results in a preserved to slightly elevated cardiac index postflight. A slightly elevated cardiac index with little change in total peripheral resistance (Figure 7) results in a slight elevation of mean arterial pressure postflight in both the supine and standing positions (Figure 8). These slight elevations in blood pressure persist for several days postflight. PASSIVE
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the elevated heart rate response immediately upon landing as well as the further accentuated heart rate response in the standing position. With just several days of recovery after these short flights, the heart rate response appears to be similar to preflight levels. Since from our previous investigations baroreflex function had not significantly changed this early in our crewmembers, a major portion of this alteration in hemodynamics still may relate to relative intravascular volume depletion. Figure 10 illustrates the end diastolic volume index, which can also be thought of as the filling volume of the left heart. The diastolic volume has been uniformly found to be depressed postflight compared to preflight, both in the supine and the standing positions. FIGURE 10 PASSIVE STAND TEST SHUTTLE OATA
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Cardiac index, in turn, although slightly decreased in the supine position during the immediate postflight period, does appear to be minimally elevated immediately postflight and persistently elevated for several days while in the standing position. More significantly, however, the heart rate response postflight (Figure 9) clearly shows
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Conclusions In summary, we believe that the cardiovascular adaptation process to space flight has at least two phases, but may indeed have three or more phases. The first of these phases is a volume redistribution and volume regulation phase. It begins immediately upon institution of space flight and has its most profound effects during the first 24 hours, but actually continues for up to perhaps the first 5 days or so of flight. Subsequent to this period of time there are secondary adaptations which are considered to be neurohumoral in origin and effect orthostatic stability profoundly. One measure of this adaptation has been described by carotid baroreflex function. These changes are hypothesized to begin early in space flight and may have additive effects with volume depletion in producing orthostatic intolerance during the end of the first week of flight. The time course of this neurohumoral adaptation is not clear at this point, although it is suspected that it is complete after three weeks of space flight. The subsequent phases of cardiovascular adaptation are not well delineated in U.S. data. They may involve further neurohumoral response, or interactions with other body systems, and can involve biochemical or ultrastructural alterations. Future investigations will be needed to determine these answers. The recovery period of the cardiovascular system after being exposed to space flight appears to be somewhat proportional to the duration of flight. Certainly most parameters return to normal values within one week after flight for flight durations of one week or less. Soviet and U.S. data suggest that longer missions require longer recovery times. The patterns and specifics of these recoveries have not been conclusively
described yet. However, it does appear clear that the process is not a linear one. References 1. Nicogossian, A. E., Huntoon, C. L., & Pool, S. L. (Eds.): Space Phvsiology and ~ , 2nd Edition; Lea and Febiger, Philadelphia (1989). 2. Sandier, H.: Effects of bedrest and weightlessness on the heart. In: Hearts and Heartlike Orcans. G. H. Bourne (Ed.), New York: Academic Press, Vol. 2 (1980). 3. Nicogossian, A. E., Sulzman, F., Radtke, M. & Bungo, M. Assessment of the efficacy of medical countermeasures in space flight. Acta Astronauti~a. 17(2): 195-
198 (1988). 4. Bungo, M. W., Charles, J. B., and Johnson Jr., P. C." Cardiovascular deconditioning during space flight and the use of saline as a countermeasure to orthostatic intolerance. Aviat. Space Environ. M ~ . 56, 985-990 (1985). 5. Cintron, N. M., Lane, W. H., and Leach, C. S.: Metabolic consequences of fluids induced by microgravity. Physiologist 33, S-16-S-19 (1990). 6. Grigoriev, A. T.: Correction of changes in fluid electrolyte metabolism in manned space flights. Aviat. Spa~e Environ. Med. 54, 318-323 (1983). 7. Leach, C. S.: Fluid control mechanism in weightlessness. Aviat. SPace Envir. Med. 58 (9, Suppl.): A74-79 (1987). 8. Fritsch,T. M., Charles, J. B., Eckberg, D.L., Bernett, B. S., and Bungo, M.W.: Effects of short duration space flight on human carotid baroreceptor cardiac reflex. FASEB Journal 4. A429 (1990).