Section 1 Cardiovascular Deconditioning E X T E N D E D D U R A T I O N O R B I T E R M E D I C A L P R O J E C T 1 Cardiovascular Deconditioning John B. Charles, Janice M. Fritsch-Yelle, Peggy A. Whitson, Margie L. Wood, Troy E. Brown, and G. William Fortner, Cardiovascular Laboratory, Johnson Space Center, Houston, TX BACKGROUND was to evaluate possible countermeasures. The Cardio- vascular EDOMP studies involved parallel descriptive, Spaceflight causes adaptive changes in cardiovascu- mechanistic, and countermeasure evaluations (Table 1-1). lar function that may deleteriously affect crew health and safety [1, 2, 3, 4, 5]. Over the last three decades, symp- GOAL 1 – DESCRIPTIVE STUDIES toms of cardiovascular changes have ranged from post- flight orthostatic tachycardia and decreased exercise Introduction capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented Before EDOMP, data describing changes in basic symptom of cardiovascular dysfunction, postflight ortho- cardiovascular parameters during and after spaceflight static intolerance, has affected a significant percentage of were sparse and equivocal, and were sometimes only U.S. Space Shuttle astronauts [6, 7, 8, 9]. Problems of reported as case studies. Because of the competition for cardiovascular dysfunction associated with spaceflight in-flight resources, many experiments were often sched- are a concern to NASA. This has been particularly true uled on the same crew members, even though one study during Shuttle flights where the primary concern is the may have interfered with the measurements of another. crew’s physical health, including the pilot’s ability to Because of these limitations, reports were inconsistent, land the Orbiter, and the crew’s ability to quickly egress and a good representative data base did not exist. Even and move to safety should a dangerous condition arise. such a basic parameter as heart rate had been reported to The study of astronauts during Shuttle activities is be increased, decreased, and unchanged during space- inherently more difficult than most human research [8]. flight. The main objective of the EDOMPcardiovascular Changes in diet, sleep patterns, exercise, medications, descriptive studies was to correct this deficit by collect- and fluid intake before and during spaceflight missions ing data; and by monitoring heart rate, blood pressure, are difficult to control. Safety restrictions make many cardiac dysrhythmias, cardiac function, and orthostatic standard research protocols inadvisable. Data collections intolerance, consistently and with a large enough number must occur without disruption of primary mission objec- of subjects to make meaningful conclusions. tives. Hardware malfunctions during in-flight data col- lections affect the quantity and/or quality of resulting Methods and Materials data. Concurrent investigations may confound interpreta- tion of both studies. Consequently, sample sizes have The first descriptive study was conducted as been small and results have lacked consistency. Before Detailed Supplementary Objective (DSO) number 463. the Extended Duration Orbiter Medical Project This study employed 24-hour Holter monitor recordings (EDOMP), there was a lack of normative data on before flight, during flight, and after flight on five crew changes in cardiovascular parameters during and after members to document any occurrence of in-flight cardiac spaceflight. The EDOMPfor the first time allowed stud- dysrhythmias [10]. ies on a large enough number of subjects to overcome The second descriptive study (DSO 602) employed some of these problems. Holter monitors as well as automatic blood pressure There were three primary goals of the Cardiovascular devices to monitor heart rate, cardiac arrhythmias, and EDOMP studies. The first was to establish, through arterial pressure for 24-hour periods before, during, and descriptive studies, a normative data base of cardiovascu- after flight [10]. The subjects were 12 astronauts who flew lar changes attributable to spaceflight. The second goal missions lasting from 4 to 14 days. During data collections was to determine mechanisms of cardiovascular changes the electrocardiogram was recorded continuously, using resulting from spaceflight (particularly orthostatic the Holter monitor, and blood pressure was taken auto- hypotension and cardiac rhythm disturbances). The third matically every 20 minutes when the subjects were awake, 1-1 Table 1-1. Cardiovascular EDOMPstudies Descriptive Studies Mechanistic Studies Countermeasure Evaluations In-flight Holter Monitoring Baroreflex Function (467) In-flight Lower Body (463) 5 Subjects PI1 16 Subjects PI1 Negative Pressure (478) 13 Subjects PI1 In-flight Arterial Pressure Baroreflex/Autonomic Control LBNPCountermeasure and Holter Monitoring (602) of Arterial Pressure (601) (623) 12 Subjects PI1 12 Subjects PI2 16 Subjects PI2 Cardiac Function (466) Neuroendocrine Responses to Hyperosmotic Fluid 32 Subjects PI1 Standing (613) 24 Subjects Countermeasure (479) PI3 23 Subjects PI1 Orthostatic Function during Cardiovascular and Cerebro- In-flight Use of Entry, Landing and Egress vascular Responses to Standing Fludrocortisone (621) (603) 34 Subjects PI1 (626) 40 Subjects PI2 16 Subjects PI2 Key to Principal Investigators: PI1 John B. Charles PI2 Jan M. Fritsch-Yelle PI3 Peggy A. Whitson and every 30 minutes during sleep. Subjects maintained attached to the upper torso of the LES to document normal routines, both on the ground and in flight. changes in body posture. The following parameters were In the third descriptive study (DSO 466), 32 astro- derived from the collected data: (1) heart rate, (2) sys- nauts on short duration missions (4-5 days in space) were tolic, diastolic, and mean arterial pressure, and (3) pulse studied with two-dimensionally directed M-mode pressure. These values were compiled for several time echocardiography to determine the effects of spaceflight periods during the preflight and in-flight testing period. on cardiac volume, cardiac function, and cardiac mass These were (1) preflight seated and standing values with [11]. Heart rate, blood pressure, and echocardiograms the g-suit inflated to the expected in-flight level, (2) in were obtained in the supine and standing positions before flight prior to onset of gravity, (3) at the onset of gravity, and after flight. M-mode echocardiograms were inter- (4) at peak gravity during entry, (5) at touchdown, and preted according to American Society of Echocardiogra- (6) seated and standing measurements during the first phy (ASE) measurement conventions [12]. Cardiac stand [15]. volumes and ejection fraction were derived by using the Teichholz formula [13]. Myocardial mass index was sub- Results sequently determined from a modification of the ASE basic formula for left ventricular mass. The mean veloc- There were several important findings in the first ity of circumferential fiber shortening was estimated by two studies (DSO 463 and 602). First, heart rate, dias- the method of Cooper et al. [14]. tolic pressure, and their variabilities were reduced during In the fourth descriptive study (DSO 603), the stan- spaceflight (Figures 1-1 and 1-2). Second, the diurnal dard Shuttle launch and entry pressure suit (LES) was variations of both heart rate and diastolic pressure were modified to include a biomedical instrumentation port reduced during spaceflight. Third, monitoring records that would allow physiological signals to be monitored demonstrated that spaceflight did not increase dysrhyth- while the LES was being worn. An automatic blood pres- mias (Figure 1-3). These data are unique because they sure/heart rate monitor was used to measure the were obtained during normal 24-hour routines, rather electrocardiogram continuously and to determine heart than as a part of any in-flight experiment intervention. rate and arterial pressure at 2-minute intervals. In most Therefore, they are important for establishing a norma- cases, three 1-axis accelerometers were used to provide tive data base for cardiovascular parameters during short reference acceleration levels. Afourth accelerometer was duration spaceflight. 1-2 100 14 Preflight Inflight Postflight Preflight Inflight Postflight e nut * pm 11 s/mi 80 R, b beat * * * of H 8 ate, 60 ev. * * eart r Std. d 5 H 40 2 140 16 *p<0.05 from * *p<0.05 from Hg preflight average Hg preflight average m m m m 12 e, P, ur B c press 120 v. of S 8 stoli d. de * Sy St 100 4 80 14 * Hg Hg * m m 11 m * * m ure, BP, * * ss 65 D 8 pre of olic dev. 5 * * ast Awake (n=12) d. Awake (n=12) Di St Asleep (n=11) Asleep (n=11) 50 2 -10 -5 Early Late +2 -10 -5 Early Late +2 Flight Day Flight Day Figure 1-1. Heart rate and arterial pressure before, Figure 1-2. Intrasubject standard deviations of heart rate during, and after flight. and arterial pressure before, during, and after flight. In the third study (DSO 466) (Table 1-2), the supine duration has no effect on myocardial contractility. Left left ventricular end diastolic volume index (EDVI) ventricular wall thickness and myocardial mass index diminished by 11% (P<0.0006) on landing day when also showed no significant changes (data not shown). compared with preflight. Similar to EDVI, supine left Arterial pressures and heart rates were monitored in ventricular stroke volume index (SVI) diminished by the fourth study (DSO 603) during landing and egress 17% (P<0.006) on landing day compared with preflight. from the Orbiter. Arterial pressure responses are shown Overall standing EDVI was less than supine, but no sig- in Figure 1-4. During spaceflight, both systolic and dias- nificant changes occurred between test days. Left ven- tolic pressure were elevated relative to preflight baseline tricular end systolic volume index (ESVI) did not values throughout the recording period, reaching their significantly change for position or time. Total peripheral highest values at peak gravity during entry, and on touch- resistance index (TPRI) was significantly greater in the down. Standing upright for the first time after landing standing position than the supine position on all test days was associated with a significant decrease, from the except landing day. Similarly, the TPRI orthostatic seated value, in systolic pressure. In seven cases, the response was less on landing day. Ejection fraction and drop was greater than 20 mmHg. This occurred in 22% velocity of circumferential fiber shortening did not of the subjects on landing day, but did not occur in any change significantly, suggesting that spaceflight of this subjects before flight. 1-3 3.0 140 Preflight Inflight Postflight <16 days, n = 34 Preflight Entry First stand e atrialons/hr 2.0 m 120 Prematurcontracti 1.0 art rate, bp 10800 00..03 n = 12 He 60 Seated Standing 0g Onset of g Max g Touchdown SeatedStanding ar 40 ntriculns/hr 0.2 Tim-6e0 of event-,3 m0in 0 30 eo mature vcontracti 0.1 * Figure 1-5. Heart rate response to entry and landing. e Pr Heart rate also reached high values at peak gravity 0.0 and touchdown. The maximum value was obtained during -10 -5 Early Late +2 the first stand (Figure 1-5). Although there was large inter- Flight Day individual variability in seated and standing heart rates, crew members generally showed a substantial increase in Figure 1-3. Premature atrial and ventricular heart rate upon standing after touchdown. There was a contractions before, during, and after flight. 70% increase in heart rate upon standing compared to the increase seen before flight. Four crew members had heart When the subjects stood after touchdown, diastolic rate values on standing that were equal to, or greater than, pressures also decreased relative to values while the sub- their maximal heart rate responses during preflight lower jects were seated. During standing in the laboratory body negative pressure tests. The highest heart rate before flight, systolic and diastolic pressures exhibited observed for any crew member was 160 bpm. Both sys- small increases. There were differences in arterial pres- tolic pressure and heart rate returned quickly to preflight sure and heart rate attributable to use of the g-suit when values during the first hour after landing, although sub- crew members who inflated the g-suit (n=24) were com- stantial differences frequently remained. pared with those who did not (n=8). Most notably, dias- tolic pressure was more adequately maintained in the Conclusions g-suit-inflated group during the post-touchdown stand- ing maneuver, compared to the non-inflated g-suit group In the first two descriptive studies, the results indi- (P< 0.006) (data not shown). cate that heart rate, blood pressure, and cardiac dys- rhythmias decreased during spaceflight when compared to preflight norms. This suggests that living in a micro- gravity environment did not cause a constant stress to the 160 cardiovascular system. However, the adaptive changes <16 days, n = 34 that occurred in response to the microgravity environ- 140 Hg Systolic ment left the astronauts ill-prepared for the cardiovascu- m lar stresses associated with return to Earth. m 120 e, Preflight Entry First stand In the third study, changes in cardiac function sur 100 occurred after short duration (4 to 5 day) spaceflights. s pre Diastolic These changes included decreased left ventricular end Arterial 864000 Seated Standing 0g Onset of g Max g Touchdown SeatedStanding dwmpieiaartsiihnpt othceleioncrmaa nlvp coveelan usosmcafu teocl aararyr nd rdeiian scdics ertoecauarntescpeaeuds teo .d chI censua trrarrtod ekdrdeai,t tiwevo oinatl,hnu admal nteei n ariecpndrpde aiatrcoseetenasdtl, reduction in the ability to augment peripheral vascular -60 -30 0 30 tone on assumption of upright posture. Changes in car- Time of event, min diovascular measurements resolved within 7 days of Figure 1-4. Systolic and diastolic pressure response landing. There were no significant changes in left to entry, landing, and egress. ventricular contractility or cardiac mass after short 1-4 Table 1-2. Cardiovascular measurements (mean ±SEM) before and after short-duration spaceflight L–10 L–5 L+0 L+(7-10) HR Supine 57 (1.8) 58 (2.0) 70* (2.2) 57 (1.8) Standing 75 (2.6) 75 (2.7) 101** (3.6) 78 (2.2) SBP Supine 105 (2.1) 106 (2.2) 109 (2.0) 106 (2.2) Standing 110 (1.7) 114† (1.7) 111 (2.2) 112 (2.0) DBP Supine 64 (2.1) 61 (2.1) 68 (2.6) 64 (2.7) Standing 79 (1.7) 79 (1.3) 81 (1.6) 80 (1.2) MAP Supine 77 (1.9) 76 (2.0) 82 (2.2) 78 (2.4) Standing 89 (1.5) 91 (1.2) 91 (1.5) 91 (1.3) PP Supine 41 (1.9) 45 (1.5) 41 (2.2) 43 (1.8) Standing 31 (1.8) 35 (1.7) 31 (2.1) 32 (1.8) EDVI Supine 59.4 (2.7) 56.1 (3.3) 52.6†† (2.7) 56.7 (2.6) Standing 41.3 (2.4) 42.6 (4.5) 35.8 (2.7) 43.0 (2.4) ESVI Supine 20.9 (1.2) 18.6 (2.0) 20.5 (1.6) 19.6 (1.6) Standing 17.3 (1.8) 16.2 (3.3) 13.4 (1.6) 17.6 (1.9) SVI Supine 38.5 (1.8) 37.5 (1.9) 32.1 (1.8) 37.1 (1.6) Standing 24.0 (1.5) 26.4 (1.9) 22.3 (1.5) 25.4 (1.1) TPRI Supine 38.4 (2.2) 38.9 (2.6) 39.7 (2.5) 39.4 (2.5) Standing 51.7 (3.8) 49.0 (6.7) 41.8 (2.0) 47.0 (2.1) EF Supine 65 (1.3) 68 (2.1) 62 (2.0) 66 (1.6) Standing 59 (3.3) 64 (5.6) 63 (2.5) 60 (2.2) LVMI 63.3 (2.5) 59.6 (2.4) 61.1 (2.2) 60.9 (2.1) *P 0.0005, cf of L-10 supine **P 0.0001, cf of L-10 standing †P 0.04, cf of L-10 standing ††P 0.0006, cf of L-10 supine P 0.006, cf of L-10 supine HR = heart rate (bpm) SBP= systolic blood pressure (mmHg) DBP= diastolic blood pressure (mmHg) MAP = mean arterial pressure (mmHg) PP= pulse pressure (mmHg) EDVI = left ventricular end-diastolic volume index (ml/m2) ESVI = left ventricular end-systolic volume index (ml/m2) TPRI = total peripheral vascular resistance index (mmHg, l/min/m2) EF = ejection fraction (%) LVMI = left ventricular mass index (g/m2) L– = launch minus L+ = landing plus 1-5 duration spaceflight. Echocardiography provided a use- next seven heart beats, the pressure stepped down sequen- ful noninvasive technique for evaluation of cardiovascu- tially to 25, 10, -5, -20, -35, -50, and -65 mmHg. R-R lar physiology after spaceflight. intervals were plotted against carotid distending pressure, Analysis of results from the fourth study showed derived by subtracting the neck chamber pressure from the that entry, landing, and seat egress after Shuttle flights systolic pressure. The following variables were taken from were associated with drops in systolic pressure and the stimulus-response relationship: maximum slope, R-R increases in heart rate. These results describe a cardio- interval range of response, minimum and maximum R-R vascular system under significant stress during nominal intervals, and operational point. The operational point was entry, landing, and seat egress, and indicate that the car- the R-R interval at zero neck pressure which represented diovascular system was performing at or near its maxi- the relative hypotensive versus hypertensive buffering mum capacity in a significant fraction (20%) of the study capacity of the reflex. population. While these crew members were never clini- The second mechanistic study (DSO 601) repeated cally hypotensive, their swings in arterial pressure and the above measurements before and after spaceflight mis- heart rate indicate that they were unable to buffer arterial sions lasting 8 to 14 days [8]. In addition, 5 minutes of pressure changes as well as before flight. It is question- continuous ECG data were taken for spectral analyses of able whether sufficient reserve capacity remained to per- R-R intervals, and blood samples were drawn before the mit unaided emergency egress by these individuals. neck stimuli for analysis of plasma catecholamine levels. Two Valsalva maneuvers were performed at 30 mmHg expired pressure for 15 seconds, and two were performed at 15 mmHg expired pressure for 15 seconds. Sixteen GOAL 2 – MECHANISTIC STUDIES astronaut subjects participated in this activity, using the same schedule as the previous study. Introduction The third mechanistic study (DSO 613) measured cat- The series of EDOMP cardiovascular mechanistic echolamine levels and cardiovascular responses to stand- studies was undertaken to test the hypothesis that ortho- ing in 24 astronauts before and after spaceflight [17]. static hypotension following spaceflight is due, at least in Studies were performed 10 days before launch, on landing part, to a disruption of autonomic control of the cardio- day, and 3 days after landing. Arterial pressure, heart rate, vascular system. The series consisted of four studies. The and cardiac output were measured. Blood samples, drawn first study was a simple evaluation of carotid barorecep- at the end of a 20-minute supine rest period and after 5 tor cardiac reflex function before and after 4 to 5 days in minutes of standing, were tested for catecholamines and space. The second study tested carotid baroreflex func- plasma renin activity. tion after 8 to 14 day spaceflights, and added measure- The fourth mechanistic study (DSO 626) sought to ments of resting plasma catecholamine levels, Valsalva define differences in physiological responses of astronauts maneuvers, and spectral analyses of arterial pressure and who did or did not become presyncopal on landing day heart rate. The third study evaluated the relationship [18]. This study was performed on 40 astronauts before between plasma catecholamine levels and total periph- and after Shuttle missions of up to 16 days. The protocol eral resistance changes upon standing. The fourth study consisted of a 20-minute supine rest period, followed by a looked at integrated cardiovascular and cerebrovascular blood draw for analyses of plasma catecholamine and responses to standing, as well as the effect of reduced plasma renin activity. Plasma volume was then measured postflight plasma volume on orthostatic tolerance. All of by the carbon monoxide rebreathing (CORB) technique. these studies used data only from crew members who An enhanced stand test was then performed, and included had not taken vasoactive or autonomic medications the following: (1) echocardiographic measurements to within 12 hours, or caffeine within 4 hours of the study. obtain aortic cross sectional area, (2) continuous wave Doppler for aortic flow, and (3) beat-to-beat arterial pres- sure and ECG. All measurements were continued for 5 Methods and Materials more minutes supine and 10 minutes standing. A final The first mechanistic study (DSO 467) tested 16 blood sample was drawn at the end of standing. This entire astronaut subjects before and after 4 to 5 day spaceflight protocol was performed 30 and 10 days before launch, on missions [7, 16]. Subjects were studied 10 and 5 days landing day, and 3 and 10 days after landing. Data were before launch, on landing day, and up to 10 days after analyzed to document differences between presyncopal landing. The protocol consisted of a 20-minute supine rest and non-presyncopal astronauts. period, followed by carotid baroreceptor stimulation. A stepping motor-driven bellows was connected to a neck Results chamber to deliver stepped pulses of pressure and suction to the neck. During held expiration, the pressure was In the first study of short duration flights (DSO 467), increased to 40 mmHg and held for 5 seconds. With the the following summary data were obtained on landing 1-6 day and compared to the preflight norm (Table 1-3, Fig- 1450 ure 1-6): resting R-R intervals and standard deviations; the slope, range, and position of operational points on the 1350 carotid distending pressure; and R-R interval response relation. These variables were all reduced on landing day c e relative to preflight. Stand tests on landing day revealed ms 1250 two separate groups, differentiated by their ability to al, Preflight v maintain standing arterial pressure. This maintenance of er arterial pressure was determined by evaluating preflight R int 1150 slopes, operational points, and supine and standing R-R – R intervals, and by preflight-to-postflight changes in stand- 1050 ing systolic pressures, body weights, and operational Landing day points (Table 1-4, Figures 1-7, 1-8, and 1-9). 950 In the second study, involving longer duration flights (DSO 601), the following changes between preflight and n = 11 landing day were found: (1) orthostatic tolerance 850 decreased, (2) R-R interval spectral power in the 0.05 to 50 100 150 200 0.15-Hz band increased (Figures 1-10 and 1-11), (3) rest- Carotid distending pressure, mmHg ing plasma norepinephrine and epinephrine levels increased, (4) the slope, range, and operational point of the Figure 1-6. Carotid baroreceptor vagal-cardiac reflex carotid baroreceptor cardiac reflex response decreased responses before flight and on landing day. Closed (Table 1-5), and (5) blood pressure and heart rate responses symbols, position of operational points. Average to Valsalva maneuvers were altered (Figures 1-12 and 1- operational point was reduced significantly on land- 13). Carotid baroreceptor cardiac reflex response changes ing day, but slope and range were not. persisted for several days after landing (Table 1-5). Table 1-3. Measurements from all subjects on all test days Postflight Day Preflight Landing Day 2 3 8-10 Systolic pressure, mmHg 116±2 116±2 117±2 116±2 116±2 Diastolic pressure, mmHg 75±1 73±2 72±2 73±2 74±2 R-R interval, ms 1,123±42 965±25* 1,069±38 1,134±39 1,069±31 Standard deviation of R-R, ms 62±6 40±4* 58±6 55±5 47±5 Body weight, kg 75.6±4.0 74.4±2.4* 75.2±2.4 75.3±2.4 75.4±2.1 Baroreflex measurements Maximum slope, ms/mmHg 5.0±1.0 3.4±0.5 3.6±0.6* 3.90±0.6* 3.9±0.6* Operational point, % 48.9±3.5 29.4±4.2† 39.8±3.6 52.4±4.7 42.4±6.0 R-R interval, ms Range 243±47 182±25 177±20* 192±102* 189±27* Minimum 1,081±43 923±30* 1,036±39 1,084±35 1,037±31 Maximum 1,324±68 1,104±31* 1,213±41* 1,275±43 1,226±38* Carotid distending pressure, mmHg At minimum R-R 80±4 83±4 92±9 82±7 75±2 At maximum R-R 153±8 172±4 160±6 157±7 161±5 Values are means ±SE. All comparisons between landing day and preflight measurements used only 11 subjects; those between landing day and measurements taken 8-10 days after landing used only 12 subjects. * P< 0.05; † P< 0.01. 1-7 Table 1-4. Subjects grouped according to relative orthostatic tolerance judged by cardiovascular parameters 10 Days Before Launch Landing Day More Less More Less resistant resistant resistant resistant Weight, kg 74.30±3.3 77.20±2.9 73.86±3.3 75.76±2.9 Age, yr 42.1±2.4 43.1±1.8 Stand tests Systolic pressure, mmHg Supine 110.4±3.4 106.4±3.0 110.3±3.7 117.9±3.9 Standing 121.4±3.4 118.9±2.0 124.3±4.0 114.0±2.9 Diastolic pressure, mmHg Supine 66.0±3.0 68.6±3.2 71.8±3.8 80.9±3.8 Standing 81.0±2.6 84.7±2.0 87.7±3.4 87.7±9.1 Heart rate, beats/min Supine 58.6±2.3 51.3±2.6 67.0±2.4 66.7±2.6 Standing 76.9±3.0 66.9±3.0* 98.3±3.7 104.4±4.2 R-R interval, m Supine 1,032±10 1,205±11* 901±9 931±10 Standing 791±10 912±11* 640±9 613±12 Baroreflex measurements Maximum slope, ms/mmHg 3.7±1.5 3.2±1.2 5.0±2.0* 5.9±2.3* R-R range, ms 194±9 232±13 177±8 225±12 Operational point, % 45.8±3.3 54.4±3.4* 32.4±3.3 27.7±4.1 Values are means ±SE for 11 subjects. *P≤0.05 between groups. 40 40 and standing norepinephrine levels remained elevated 3 g = Preflight ** days after landing while epinephrine levels returned to mmH30 = Landing day 30min. preflight levels. On landing day, supine heart rate and sys- e, n = 16 ats/ tolic blood pressure were elevated 18% and 8.9%, respec- stolic pressur2100 * 2100heart rate, be thainevader l1tyI n,9r a %twthe,eh ar efennosd up credtochimat issvpttuoeadllryiyec d ((bd DltaooStoa O dtnh 6ope2t r e6pss)hrs,e ou4fwrl0ie gn cwh)r.ete wrne om ermelemv. baSteetradsn w3d8ien%rge y s tested. However, 11 were excluded for violations of test 0 0 constraints or contamination of blood samples. Of the Systolic Diastolic Heart rate remaining 29 astronauts, 8 could not complete their stand Change, standing minus supine tests on landing day because they became presyncopal. These subjects displayed arterial pressure and heart rate Figure 1-7. Preflight and landing day differences between responses to standing that were similar to those seen in standing and supine systolic and diastolic pressures adrenergic failure (Figure 1-15). On landing day, their and heart rate. Significant difference between groups: standing norepinephrine levels were significantly lower *P< 0.05; **P< 0.01. than the norepinephrine levels of the astronauts who did not become presyncopal (Table 1-6a). The failure of the sympathetic nerves to increase norepinephrine release with The third study (DSO 613) showed that on landing standing translated into lower peripheral vascular resis- day supine plasma norepinephrine and epinephrine levels tance and ultimately presyncope. Plasma volumes were not were increased 34% and 65%, respectively, from the pre- different between groups either before or after flight. flight norm, and standing norepinephrine and epinephrine There were also significant preflight differences levels were increased 65% and 91% (Figure 1-14). Supine between the presyncopal and non-presyncopal groups 1-8 20 g n di 0.05 n a s. st 0.0 5 0.04 vg upine mmH 0 stin 0.0 4 0.03 Pre- to postflight change in ssystolic pressure, --2400 nrp ==< 001..40618 u yrartibra ,rewoP00..0.000.032010 Fr0.e1quenc0y.2, Hz 0.3 0.4 PreLfalLing+dLhi(tn+1Lg(,24 +L()0,00L(5+.6..0))00(,108120),D1ay8) -60 -40 -20 0 20 Pre- to postflight change Figure 1-10. Three-dimensional plot of power spectra in operational point, percent of R-R intervals during controlled frequency breath- ing for 12 subjects, all days. Figure 1-8. Preflight-to-postflight (landing day) changes of operational points and systolic pressure responses to sfotarn adliln dga. tLai.n Cealurs rteegr raenssailoynsi cs oorfr ethlaetsieo nd actoae fifdiceinetniftise adr 2e units 7 A * n = 12 y 6 distinct groups, which have been termed less and more ar resistant to postural change. Hatched area, more resis- bitr 5 tant group. al, ar 4 ot 3 T 4 (Table 1-6b). While still well within normal ranges, the * z B H group that became presyncopal on landing day had lower 5 3 preflight supine and standing diastolic pressures and 0.1 peripheral vascular resistance than the non-presyncopal er 5 - 2 group. The supine heart rates of the presyncopal group ow 0.0 were also higher and their standing systolic pressures al p 1 v were lower. Three days after landing, norepinephrine er 2 levels and diastolic pressure were again similar in the nt C two groups (Table 1-6c). However, peripheral vascular R-R i 3 Hz1.5 resistance and systolic pressure were lower in the pre- 0. syncopal group during standing. 2 - 1 0. .5 Standing - supine pressure, mmHg--422400000 * =MnLn pe==o* s< rs86e r0 re.e0ssi5sistatan*ntt Operational point, percent--442200000 * Standing - supine heart rate, bpm--424200000 Body weight, kg--42024 * Low/high frequency 76543 DPreflight D*0a*y2s af4*ter6 lan8di1n0g Systolic Diastolic Figure 1-11. Average total power (A), power in 0.05- to 0.15-Hz band (B), 0.2- to 0.3-Hz band (C), and ratio Figure 1-9. Comparisons of preflight to landing day of low- to high-frequency power (D) throughout changes between 2 groups identified by cluster analy- study. n, no. of subjects. *P < 0.025 compared with sis. *P< 0.01. preflight. 1-9