Ode to history and celebration of space medicine: 50 years of vision from the AsMA Space Medicine Branch. Aero Medical Association.
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Biomedical subjects
Publications and source records attributed to G W Hoffler.
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We studied hemodynamic responses to alpha- and beta-receptor agonists in eight healthy men before and after 14 days of 6 degrees head-down tilt (HDT) to test the hypothesis that increased adrenoreceptor responsiveness is induced by prolonged exposure to simulated microgravity. Steady-state infusions of isoproterenol (Iso) at rates of 0.005, 0.01, and 0.02 microgram.kg-1.min-1 were used to assess beta 1- and beta 2-adrenoreceptor responsiveness. Infusions of phenylephrine (PE) at rates of 0.25, 0.50, and 1.00 microgram.kg-1.min-1 were used to assess responsiveness of alpha 1-vascular adrenoreceptors. Slopes calculated from linear regressions between Iso and PE doses and changes in beat-to-beat heart rate, blood pressure, and leg vascular resistance (occlusion plethysmography) for each subject were used as an index of alpha- and beta-adrenoreceptor responsiveness. HDT increased the slopes of heart rate (1,056 +/- 107 to 1,553 +/- 83 beats micrograms-1.kg-1.min-1; P = 0.014) and vasodilation (-469 +/- 111 to -1,446 +/- 309 peripheral resistance units.microgram-1.kg-1.min-1; P = 0.0224) to Iso infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that simulated microgravity causes selective increases in beta 1- and beta 2-adrenoreceptor responsiveness without affecting alpha 1-vascular adrenoreceptor responses.
INTRODUCTION: The purpose of this study was to determine the effectiveness of a USAF anti-gravity suit (G-suit) on the stability of a patient with chronic orthostatic hypotension. METHODS: A 37-yr-old female with a history of insulin-dependent diabetes mellitus (IDDM) and symptomatic orthostasis was evaluated and the results were compared with those of non-diabetic controls, matched for age, height, and weight. Cardiac vagal tone was assessed by determination of standard deviation of 100 R-R intervals (R-R SD). We assessed the carotid-cardiac baroreflex response by plotting R-R intervals (ms) at each of eight neck pressure steps with their respective carotid distending pressures (mm Hg). Heart rate and blood pressure were recorded in response to the Valsalva maneuver (VM) performed at an expiratory pressure of 30 mmHg to assess integrated baroreflex responses. Blood pressures and heart rate were measured during three 5-min stand tests to assess orthostatic responses: a) without G-suit; b) with noninflated G-suit; and c) with inflated G-suit (50 mm Hg). RESULTS: The IDDM patient had minimal baseline cardiac vagal tone (R-R SD = 8.5 ms) compared with the average response of a control group of 24 subjects with orthostatic stability (R-R SD = 67.2 +/- 7.1 ms). Carotid-cardiac baroreflex response was virtually non-existent in the IDDM patient (Gain = 0.06 ms.mm Hg-1) compared to the control subjects (4.4 +/- 0.8 ms.mm Hg-1). VM responses corroborated the lack of cardiac baroreflex response in the IDDM patient, while blood pressure changes during the VM were similar to those of the controls. Upon standing, the IDDM patient demonstrated severe orthostatic hypotension (90 mm Hg SBP) and tachycardia without the G-suit. The G-suit, with and without pressure, reduced hypotension and tachycardia during standing. CONCLUSION: These results demonstrate successful application of Air Force technology as a useful alternative to pharmacologic intervention in the treatment of a patient with autonomic dysfunction leading to supine hypertension and orthostatic hypotension.
Increased sensitivity of end-organ responses to neuroendocrine stimuli as a result of prolonged exposure to the relative inactivity of microgravity has recently been hypothesized. This notion is based on the inverse relationship between circulating norepinephrine and beta-adrenoreceptor sensitivity. Beta-adrenoreceptor activity is reduced in individuals who have elevated plasma norepinephrine as as a result of regular exposure to upright posture and physical exercise. In contrast, adrenoreceptor hypersensitivity has been reported in patients with dysautonomias in which circulating catecholamines are absent or reduced. Taken together, these studies and the observation that circulating plasma norepinephrine has been reduced during spaceflight and in groundbased simulations of microgravity prompt the suggestion that adrenoreceptor hypersensitivity may be a consequence of the adaptation to spaceflight. We conducted an experiment designed to measure cardiovascular responses to adrenoreceptor agonists in human subjects before and after prolonged exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that adaptation to microgravity increases adrenoreceptor responsiveness, and that this adaptation is associated with reduced levels of circulating norepinephrine.
Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake (VO2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6 degrees) head-down tilt (HDT), each subject underwent graded LBNP to -6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither VO2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge.
Experiments during spaceflight and its groundbase analog, bedrest, provide consistent data which demonstrate that numerous changes in cardiovascular function occur as part of the physiological adaptation process to the microgravity environment. These include elevated heart rate and venous compliance, lowered blood volume, central venous pressure and stroke volume, and attenuated autonomic reflex functions. Although most of these adaptations are not functionally apparent during microgravity exposure, they manifest themselves during the return to the gravitational challenge of earth's terrestrial environment as orthostatic hypotension and instability, a condition which could compromise safety, health and productivity. Development and application of effective and efficient countermeasures such as saline "loading," intermittent venous pooling, pharmacological treatments, and exercise have become primary emphases of the space life sciences research effort with only limited success. Successful development of countermeasures will require knowledge of the physiological mechanisms underlying cardiovascular adaptation to microgravity which can be obtained only through controlled, parallel groundbased research to complement carefully designed flight experiments. Continued research will provide benefits for both space and clinical applications as well as enhance the basic understanding of cardiovascular homeostasis in humans.
We compared high-density lipoprotein cholesterol (HDL-C) and other blood and cardiovascular variables of subjects when they had been fasting overnight to those values when they had eaten breakfast. The subjects were 47 men (24 to 70 years) and 34 women (23 to 63 years) who visited our laboratory on two occasions, once fasting and once after breakfast, at the same time of the morning, exactly 1 week apart. Systolic (SBP) and diastolic (DBP) pressures and heart rates (HR) were recorded, and 24-ml blood samples were obtained from an antecubital vein and analyzed for hemoglobin (Hgb), hematocrit (Hct), HDL-C, total cholesterol (T Chol), triglycerides (Trig), total calcium (T Ca), ionized calcium (Ca++), and phosphorus (P). When subjects were fasting, their SBP, HR, Trig, T Ca, and Ca++ were lower than when they had eaten breakfast. SBP, DBP, Hgb, and Trig of the women were lower than those of the men; and HDL-C and phosphorus of the women were higher. Several correlations between variables were significant only when subjects were fasting. These were SBP with age, Hct with T Ca, and T Chol with Trig. Several correlations were significant only for one sex. For the women only, SBP, DBP, and HR were correlated with T Chol, and Trig and HDL-C were correlated with T Ca. For the men only, Hgb was correlated with HDL-C, Trig, T Ca, and P; and HDL-C was correlated with Trig.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of orthostatic hypotension can increase after prolonged exposure to chair rest and bedrest and is associated with post-bed rest impairment of the carotid-cardiac baroreflex response. We therefore hypothesized that the hypotension observed in humans confined to wheelchairs may be manifested by a reduced baroreflex sensitivity. We compared baroreflex responses of 16 wheelchair-dependent (WCD) quadriplegics with those of 15 able-bodied subjects (ABS) matched for age, height, and weight. Beat-to-beat R-R intervals were measured during application of graded pressures from 40 to -65 mmHg using a neck chamber for noninvasive stimulation of the carotid baroreceptors. Changes of R-R intervals were plotted against carotid distending pressures. The maximum slope of the stimulus-response relationship was greater (P less than 0.0001) in ABS (6.1 +/- 0.6 ms/mmHg) than in WCD (2.6 +/- 0.4 ms/mmHg). The range of the R-R interval response, i.e., the capacity to buffer blood pressure changes, was only 138 +/- 19 ms in WCD compared with 253 +/- 19 ms in ABS (P less than 0.001). Mean sitting systolic-to-diastolic blood pressures in WCD (92/60 mmHg) were less (P less than 0.0001) than in ABS (120/77 mmHg), although there were no significant differences between groups in supine resting blood pressures. Chronic loss of stimulation to carotid baroreceptors by routine standing posture is associated with attenuated sensitivity and reduced buffer capacity of the arterial baroreflex and hypotension during sitting in WCD patients.
We studied cardiovascular responses to lower-body negative pressure (LBNP) following 1 hour (h) of 6 degrees head-down tilt to determine whether a redistribution of blood volume toward the central circulation modifies the subsequent response to orthostatic stress. Responses of 12 men, ages 30-39 years, were evaluated by electrocardiography, impedance cardiography, sphygmomanometry, and measurement of calf circumference. During the LBNP that followed head-down tilt--as compared with control LBNP (no preceding head-down tilt)--subjects had smaller stroke volume and cardiac output, greater total peripheral resistance, and less calf enlargement. These differences reflect differences in the variables immediately preceding LBNP. Magnitudes of the responses from pre-LBNP to each pressure stage of the LBNP procedure did not differ between protocols. Mean and diastolic arterial pressures were slightly elevated after LBNP-control, but they fell slightly during LBNP post-tilt. These cardiovascular responses to simulated gravitational stress following head-down tilt may reflect the manner in which adaptation to microgravity affects subsequent responses to orthostatic stress on return to Earth.
Leg compliance is "causally related with greater susceptibility" to orthostatic stress. Since peak O2 uptake (peak VO2) and muscle strength may be related to leg compliance, we examined the relationships between leg compliance and factors related to muscle size and physical fitness. Ten healthy men, 25-52 yr, underwent tests for determination of vascular compliance of the calf (Whitney mercury strain gauge), peak VO2 (Bruce treadmill), calf muscle strength (Cybex isokinetic dynamometer), body composition (densitometry), and anthropometric measurements of the calf. Cross-sectional areas (CSA) of muscle, fat, and bone in the calf were determined by computed tomography scans. Leg compliance was not significantly correlated with any variables associated with physical fitness per se (peak VO2, calf strength, age, body weight, or composition). Leg compliance correlated with calf CSA (r = -0.72, P less than 0.02) and calculated calf volume (r = -0.67, P less than 0.03). The most dominant contributing factor to the determination of leg compliance was CSA of calf muscle (r = -0.60, P less than 0.06), whereas fat and bone were poor predictors (r = -0.11 and 0.07, respectively). We suggest that leg compliance is less when there is a large muscle mass providing structural support to limit expansion of the veins. This relationship is independent of aerobic and/or strength fitness level of the individual.
Responses of 21 women and 29 men (29-56 yr of age) to -50 Torr lower body negative pressure (LBNP) were examined for differences due to sex or age. Responses to LBNP were normal, including fluid shift from thorax to lower body, increased heart rate and peripheral resistance, and decreased stroke volume, cardiac output, and Heather index of ventricular function. Mean arterial blood pressure did not change. Comparison of responses of the women to responses of an age-matched subset of the men (n = 26) indicated the men had larger relative increases in calf circumference and greater increases in peripheral resistance during LBNP than the women, whereas the women experienced greater increases in thoracic impedance and heart rate. Analyses of responses of the 29 men for age-related differences indicated older subjects had greater increases in peripheral resistance and less heart rate elevation in response to LBNP (P less than 0.05 for all differences, except sex-related heart rate difference, where P less than 0.10). Based on these data and the data of other investigators, we hypothesize the age-related circulatory differences in response to LBNP are due to a reduction in vagal response and a switch to predominant sympathetic nervous system influence in older men. We cannot exclude the possibility that diminished responsiveness in the afferent arm of the baroreceptor reflex also plays a role in the attenuated heart rate response of older men to LBNP.
We have investigated the pattern of fluid redistribution and cardiovascular responses during graduated orthostatic stress. Twelve men, age 30-39 yr, underwent a 25-min lower-body negative pressure (LBNP) test protocol that involved sequential stages of LBNP at -8 mmHg (1 min), -16 mmHg (1 min), -30 mmHg (3 min), -40 mmHg (5 min), -50 mmHg (5 min), -40 mmHg (5 min), -30 mmHg (3 min), -16 mmHg (1 min), and -8 mmHg (1 min). Data were recorded at the end of each stage. For many measured variables values during the descending phase of LBNP (-8 to -40 mmHg) were significantly different from values during the ascending phase of (-40 to -8 mmHg). These differences appear to be due to a component of fluid translocation that occurs during LBNP and cannot be reversed within the duration of the procedure. We hypothesize that this slowly reversed component is sequestration of fluid in the interstitial and lymphatic compartments. In contrast, venous pooling is a rapidly reversible component of fluid movement during LBNP. A scheme describing fluid and cardiovascular responses to LBNP based on these data and the data of other investigators is presented.
High aerobic fitness may be associated with impaired responsiveness to orthostatic challenge. This could be detrimental to astronauts returning from spaceflight. Thus, we examined the cardiovascular responses of a group of 45 healthy women to graded lower body negative pressure (LBNP) through 5 min at -50 mm Hg or until they become presyncopal. The ages (range = 23-43 years, mean = 30.4) and peak aerobic capacities (range = 23.0-55.3 ml.kg-1.min-1, mean = 37.8) of these subjects paralleled those of the women astronauts. We monitored heart rate, stroke volume, cardiac output, Heather index of contractility, arterial pressure, peripheral resistance, change in calf circumference, and thoracic impedance (ZO)--a measure of fluid in the chest. The women in this study exhibited the same response pattern to LBNP as previously reported for male subjects. VO2peak of the six subjects who became presyncopal was not different from VO2peak of the tolerant subjects. At rest, only systolic and mean arterial pressures were significantly correlated with VO2peak. Percent changes in calf circumference (i.e. fluid accumulation in the legs) at -30 and -40 mm Hg were the only responses to LBNP significantly related to VO2peak. The greater pooling of blood in the legs during LBNP by women with higher aerobic fitness, and lower percent body fat may be related to more muscle tissue and vasculature in the legs of the more fit subjects. These data indicated that orthostatic tolerance is not related to aerobic capacity in women, and orthostatic tolerance need not be a concern to aerobically fit women astronauts.
The cardiovascular response to 1 h of 6 degrees head-down tilt was studied in 12 male subjects, ages 30-39 years, to simulate the early effects of weightlessness. Fluid shifts, hemodynamic variables, and indices of myocardial contractility were evaluated by utilizing electrocardiography, systolic time intervals, impedance cardiography, sphygmomanometry, and measurement of calf circumference. Most cardiovascular variables remained stable throughout the initial 30 min of the protocol, even though translocation of fluid from the legs to the thorax commenced immediately with the onset of head-down tilt. In contrast, minutes 30-60 were characterized by reduced stroke volume, cardiac output, mean stroke ejection rate, and Heather Index concomitant with an elevation in mean arterial pressure. Intrathoracic fluid volume continued to increase while leg volume continued to decrease. This latter physiological response suggests intrathoracic sequestration of fluid volume; blood was apparently redistributed to the pulmonary circulation rather than being retained in the great veins.
Lower body negative pressure (LBNP) has provided a method for studying cardiovascular responses in men while simulating a return to the stresses of 1-G following space flight. In this study, we have monitored responses of women to the stresses provided by LBNP. There were 20 women, 23-43 years, each tested in the follicular and luteal phases of the menstrual cycle. Variables were recorded during supine control; at -30, -40, -50 mm Hg LBNP; immediately after pressure release; and after 5 min recovery. There were no significant differences in response to LBNP between the two menstrual phases. During LBNP calf circumference was enlarged; transthoracic impedance was increased; stroke volume, left ventricular ejection time, the Heather Index of contractility and systolic pressure were reduced; total peripheral resistance was elevated; and cardiac output fell despite a rise in heart rate. Differences in cardiovascular variables between 0 mm Hg LBNP and -50 mm Hg LBNP were generally similar to reported differences between supine and standing. The responses of these women to LBNP were qualitatively similar to those reported for the Apollo astronauts and other male subjects. These women appeared to compensate with a greater heart rate response; however, the net cardiovascular compensation as determined from arterial pressure appears to be similar in men and women.
This study investigated the potential value of specific cellular responses to acute and chronic exercise as indices of physical fitness. Muscle enzymatic and hemolytic responses following a progressive cycle-ergometer test to maximal aerobic capacity were studied in 12 women and 12 men, aged 27 to 55 yr, who had been previously assigned to "high" and "low" fitness groups. Venous blood samples were obtained at rest prior to the cycle test, immediately following maximal effort, and 1, 2, 4, 6 and 24 h post exercise. The samples were analyzed for hematocrit (Hct), hemoglobin (Hb), lactate dehydrogenase (LDH), serum glutamic oxalacetic transaminase (SGOT), creatine phosphokinase (CK), CK isoenzymes, and haptoglobin (Hapt). Hemoglobin and Hct were the only variables to rise significantly (P less than 0.05) following exercise, and at all sampling times were significantly lower in the women compared with the men; CK was constituted in the MM isoenzyme band at all times; and Hapt levels were significantly lower in high-fitness men and women as compared with low-fitness men and women. These results indicate that one progressive test to maximal aerobic capacity is not sufficient to induce significant muscle enzymatic or hemolytic stress responses. They do suggest, however, that a chronic hemolytic condition exists as a result of aerobic conditioning activity.
Results of orthostatic evaluations of the crew of Skylab 3 with lower body negative pressure (LNBP) stress tests during their 59-d mission are reported. The test protocol was identical to that used in the first manned Skylab mission and the latter Apollo flights. Except for an inflight increase (rather than a decrease) in resting heart rates, results were essentially parallel to those observed in crewmen of the shorter Skylab 2 mission. Exaggerated elevations in heart rate and decreases in pulse pressure during LBNP stress inflight and immediately postflight corresponded to lowered orthostatic tolerance. Large decrements in resting calf size inflight and in total leg volume postflight indicated significant headward fluid shifts as had already been seen in the Skylab 2 crewmen. In addition, decreases in calf circumference gave no certain indication of a plateau over the 59 d inflight. On the other hand, percentage volume increase in calf size during LBNP stress inflight was greater than those in either preflight or postflight tests. Hypotheses elaborated after the Skylab 2 mission seem to have been substantiated, but several enigmas await data from the last and longer mission for clarification.