Evaluation of cardiovascular risks of spaceflight does not support the NASA bioastronautics critical path roadmap

INTRODUCTION: Occurrence of serious cardiac dysrhythmias and diminished cardiac and vascular function are the primary cardiovascular risks of spaceflight identified in the 2005 NASA Bioastronautics Critical Path Roadmap. METHODS: A review of the literature was conducted on experimental results and observational data obtained from spaceflight and relevant ground simulation studies that addressed occurrence of cardiac dysrhythmias, cardiac contractile and vascular function, manifestation of asymptomatic cardiovascular disease, orthostatic intolerance, and response to exercise stress. RESULTS: Based on data from astronauts who have flown in space, there is no compelling experimental evidence to support significant occurrence of cardiac dysrhythmias, manifestation of asymptomatic cardiovascular disease, or reduction in myocardial contractile function. Although there are post-spaceflight data that demonstrate lower peripheral resistance in astronauts who become presyncopal compared with non-presyncopal astronauts, it is not clear that these differences are the result of decreased vascular function. However, the evidence of postflight orthostatic intolerance and reduced exercise capacity is well substantiated by both spaceflight and ground experiments. Although attenuation of baroreflex function(s) may contribute to postflight orthostatic instability, a primary mechanism of orthostatic intolerance and reduced exercise capacity is reduced end-diastolic and stroke volume associated with lower blood volumes and consequent cardiac remodeling. CONCLUSION: Data from the literature on the current population of astronauts support the notion that the primary cardiovascular risks of spaceflight are compromised hemodynamic responses to central hypovolemia resulting in reduced orthostatic tolerance and exercise capacity rather than occurrence of cardiac dysrhythmias, reduced cardiac contractile and vascular function, or manifestation of asymptomatic cardiovascular disease. These observations warrant a critical review and revision of the 2005 Bioastronautics Critical Path Roadmap.     

航天员常见症状的用药与体位性低血压的关系

目的对航天员在航天飞行中与航天飞行后常见症状的用药与体位性低血压的关系进行综述。资料来源与选择该领域公开发表的相关研究论文、综述、报告汇编（包括美国国家航空航天局网站上的公开文献）和著作。资料引用引用公开发表的报刊文献32篇,报告汇编5篇,和著作12部。资料综合航天员在航天飞行中与航天飞行后最常出现的症状分别为头晕、呕吐（航天运动病）、头痛、背部疼痛、失眠和晕厥,对于这些症状的西药治疗有时会对心血管系统产生不良影响。止吐药异丙嗪伴有抑制去甲肾上腺素、肾素、醛固酮分泌的作用;安眠药替马西泮具有松弛骨骼肌张力的作用;升压药氟氢可的松具有抑制去甲肾上腺素分泌的作用。这些药物都会引起血管收缩下降,水钠储留减少,回心血量降低从而造成体位性低血压。结论航天员常见症状的西药疗法常会引起体位性低血压。中国可以运用中药针灸和少量的西药复合疗法来防治航天员的常见症状,从而减少西药对人体的不良作用。     

Aerobic fitness in women and responses to lower body negative pressure

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.     

Hemodynamic effects of midodrine after spaceflight in astronauts without orthostatic hypotension

INTRODUCTION: Orthostatic hypotension and presyncope are common and potentially serious risks for astronauts returning from space. Susceptible subjects fail to generate an adequate adrenergic response to upright posture. The alpha-1 adrenergic agonist, midodrine, may be an effective countermeasure. We tested the hypothesis that midodrine would have no negative hemodynamic effect on healthy astronauts returning from space. METHODS: Five male astronauts participated in preflight and post-flight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing approximately 1 h before testing. RESULTS: None of these astronauts exhibited orthostatic hypotension or presyncope before or after either flight. Midodrine did not cause any untoward reactions in these subjects before or after flight; in fact, a modest beneficial effect was seen on postflight tachycardia (p = 0.036). DISCUSSION: These data show that midodrine protected against post-spaceflight increases in heart rate without having any adverse hemodynamic effects on non-presyncopal, male astronauts. Among these subjects, midodrine was a safe cardiovascular countermeasure.     

The exercise and environmental physiology of extravehicular activity

Extravehicular activity (EVA), i.e., exercise performed under unique environmental conditions, is indispensable for supporting daily living in weightlessness and for further space exploration. From 1965-1996 an average of 20 h x yr(-1) were spent performing EVA. International Space Station (ISS) assembly will require 135 h x yr(-1) of EVA, and 138 h x yr(-1) is planned for post-construction maintenance. The extravehicular mobility unit (EMU), used to protect astronauts during EVA, has a decreased pressure of 4.3 psi that could increase astronauts' risk of decompression sickness (DCS). Exercise in and repeated exposure to this hypobaria may increase the incidence of DCS, although weightlessness may attenuate this risk. Exercise thermoregulation within the EMU is poorly understood; the liquid cooling garment (LCG), worn next to the skin and designed to handle thermal stress, is manually controlled. Astronauts may become dehydrated (by up to 2.6% of body weight) during a 5-h EVA, further exacerbating the thermoregulatory challenge. The EVA is performed mainly with upper body muscles; but astronauts usually exercise at only 26-32% of their upper body maximal oxygen uptake (VO2max). For a given ground-based work task in air (as opposed to water), the submaximal VO2 is greater while VO2max and metabolic efficiency are lower during ground-based arm exercise as compared with leg exercise, and cardiovascular responses to exercise and training are also different for arms and legs. Preflight testing and training, whether conducted in air or water, must account for these differences if ground-based data are extrapolated for flight requirements. Astronauts experience deconditioning during microgravity resulting in a 10-20% loss in arm strength, a 20-30% loss in thigh strength, and decreased lower-body aerobic exercise capacity. Data from ground-based simulations of weightlessness such as bed rest induce a 6-8% decrease in upper-body strength, a 10-16% loss in thigh extensor strength, and a 15-20% decrease in lower-body aerobic exercise capacity. Changes in EVA support systems and training based on a greater understanding of the physiological aspects of exercise in the EVA environment will help to insure the health, safety, and efficiency of working astronauts.     

Midodrine prescribed to improve recurrent post-spaceflight orthostatic hypotension

Many astronauts exhibit post-spaceflight orthostatic hypotension due to inadequate norepinephrine release when in an upright posture. We hypothesized that an alpha1-adrenergic agonist, midodrine, would be an effective countermeasure. A female astronaut, who had problems with postflight orthostatic hypotension after a previous flight, consumed 10 mg midodrine after a subsequent flight, prior to her tilt test. Hemodynamic variables were compared between the two flights. Midodrine prevented severe falls in stroke volume, cardiac output and systolic pressure, and severe increases in heart rate without increasing vascular resistance, thus preventing orthostatic hypotension. This is the first report showing that midodrine has the potential to improve post-spaceflight orthostatic hypotension and suggesting that reduced venous return contributes to the etiology.     

Presyncopal/non-presyncopal outcomes of post spaceflight stand tests are consistent from flight to flight

INTRODUCTION: The overall prevalence of orthostatic hypotension after short duration (6-18 d) spaceflight is 20% with existing countermeasures. However, it is not known if the outcomes of stand tests for orthostatic tolerance are consistent within individuals on subsequent flights, or if first time fliers are more (or less) likely to experience orthostatic hypotension and presyncope than are veteran astronauts. METHODS: There were 50 astronauts who were studied retrospectively. Stand test data, which had been collected before and after spaceflight, were compared from at least two flights for each astronaut. For 25 of these astronauts, their first flight in this database was also their first spaceflight. For the remaining 25, their first flight in this database was their second, third, or fourth flight, as data were available. RESULTS: No subject became presyncopal during preflight testing. Of the 50 subjects, 45 (90%) had the same outcome on their first and second flights of this study. Of 14 subjects on whom we had data from a third mission, 12 had the same stand test outcome on all 3 flights (86% same outcome across 3 flights). There was no correlation between flight duration and orthostatic tolerance (r = 0.39). DISCUSSION: These data support the idea that astronauts are predisposed to orthostatic tolerance/intolerance after spaceflight and that this predisposition is not altered by subsequent flights. Flight durations within this data set did not alter the likelihood of orthostatic intolerance and rookie fliers were no more likely to experience orthostatic intolerance than were veteran astronauts.     

Exercise equipment used in microgravity: challenges and opportunities

A variety of physiological changes are experienced by astronauts during both short- and long-duration space missions. These include space motion sickness, spatial disorientation, orthostatic hypotension, muscle atrophy, bone demineralization, increased cancer risk, and a compromised immune system. This review focuses on countermeasures used to moderate these changes, particularly exercise devices that have been used by National Aeronautics and Space Administration astronauts over the past six decades as countermeasures to muscle atrophy and bone loss. The use of these devices clearly has shown that a microgravity environment places unusual demands on both the equipment and the human users. While it is of paramount importance to overcome microgravity-induced musculoskeletal deconditioning, it also is imperative that the exercise system (i) is small and lightweight, (ii) does not require an external power source, (iii) produces 1g-like benefits to both bones and muscles, (iv) requires relatively short durations of exercise, and (v) does not affect the surrounding structure or environment negatively through noise and/or induced vibrations.     

Winter storm warning: Snow removal may be hazardous to your (patient’s) health

Conclusions Numerous studies in persons with and without coronary artery disease have identified low levels of daily physical activity and aerobic fitness as independent risk factors for all-cause and cardiovascular mortality[21]-[23]. Thus, it appears that physical activity may either protect against or provoke SCD [24],[25], depending on the intensity of exercise, usual frequency of strenuous exertion, level of aerobic fitness, superimposed circadian, cognitive, and environmental stresses, and the presence of a diseased or susceptible heart. Selected patients, therefore, should be cautioned regarding the potentially threatening myocardial demands of manual or even automated snow removal.     

Mineral and nitrogen balance study observations: the second manned Skylab mission.

A metabolic study of the effects of space flight on various chemical elements, particularly those with special revelance to the musculoskeletal system, was carried out on the three astronauts of the SL-3 mission for 21 d preflight, during the 60 d flight phase, and for 17 d postflight. The study required of the cooperating crewmen quite constant dietary intake, continuous 24-hour urine collections and total fecal collections. Urinary calcium was significantly increased during flight in all three crewmen with man-to-man variation in pattern and amount; the degree of calcium loss was, in general, similar to that in the prior study of the 28-d Skylab flight (SL-2). The similarity to bedrest immobilization in the pattern of urinary calcium increases and of total calcium shifts suggested that calcium losses would continue for a very long time. Significant losses of nitrogen and phosphorus occurred that were associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens during flight. It was concluded that these studies give warning that capable musculoskeletal function may be significantly impaired during prolonged space flights lasting 1.5 to 3 years unless protective measures are developed.     

Potential benefits of maximal exercise just prior to return from weightlessness

The purpose of this study was to determine whether performance of a single maximal bout of exercise during weightlessness within hours of return to earth would enhance recovery of aerobic fitness and physical work capacities under a 1G environment. Ten healthy men (36-51 yr) underwent maximal supine exercise followed by upright maximal exercise before and after a 10-d bedrest period in the 6 degrees headdown position. A graded maximal supine cycle ergometer test was performed before and at the end of bedrest to simulate exercise during weightlessness. Following 3 h of resumption of the upright posture from the supine exercise test, a second maximal exercise test was performed on a treadmill to measure work capacity under conditions of 1G. Compared to before bedrest, peak VO2 decreased (p less than 0.05) by 8.7% and peak HR increased (p less than 0.05) by 5.6% in the supine cycle test at the end of bedrest. However, there were no significant changes in peak VO2 and peak HR in the upright treadmill test following bedrest. These data, based on a simulation, suggest that one bout of maximal leg exercise prior to return from 10 d of weightlessness may be adequate to restore preflight aerobic fitness and physical work capacity.     

Health- and performance-related potential of resistance training

Regular physical activity can improve cardiovascular fitness and may reduce the likelihood and debilitating effects of cardiovascular disease. Weight-training has generally been believed to have limited value in modifying risks of cardiovascular disease. Effects shown of resistance training on parameters associated with cardiovascular fitness and disease include: heart rate decreases for maximal work and recovery from short term weight-training, increased ventricular mass, and increased ventricular wall and septum thickness. Studies suggest that myocardial hypertrophy resulting from resistive training can be accompanied by positive myocardial adaptations. Blood pressure response considerations to resistive training include: similarity of resistive exercise peak response to other forms of high intensity exercise, highest blood pressures occur at or near exhaustion during maximum lifts, training appears to reduce the exercise blood pressure. Given the blood pressure responses caution is required for individuals with cardiovascular disease. Studies of high-volume weight-training indicate that small to moderate increases in aerobic power can occur in relatively short periods of time. The mechanisms by which weight-training increases VO2max is unclear. Resistive training may produce positive changes in serum lipids with the volume of training being the dependent factor. Cross-sectional and longitudinal studies of bodybuilders suggest that weight-training may beneficially alter glucose tolerance and insulin sensitivity. It appears that weight-training can increase short term high intensity endurance without a concomitant loss in performance. Resistive training increases power output and performance. Body composition has important relationships to cardiovascular fitness, strength and flexibility. It is likely that it can be affected and controlled by use of large body mass during exercise depending on training volume.     

The circulatory response to exercise: role of the peripheral pump.

The circulation of blood during upright exercise involves a two-pump system, a central cardiac pump and a peripheral pump responsible for systemic venous return. Axiomatically, the function of the two pumps must be equal, and certain evidence suggests that the peripheral pump may "drive" the circulation during exercise. Despite its potential importance to circulatory reserve and aerobic fitness, little is known regarding the determinants of the peripheral pump. Pumping function of skeletal muscle and the suction effect of the left ventricle presumably are principal factors in defining systemic venous return. This review, which focuses on data in humans, examines current information regarding the peripheral pump and its potential role as a critical determinant of maximal cardiac output, maximal oxygen uptake, and endurance fitness.     

Self-generated lower body negative pressure exercise.

BACKGROUND: Exercise during spaceflight helps prevent musculoskeletal and cardiovascular deconditioning to Earth gravity. This report evaluates the aerobic and anaerobic exercise stimulus provided by self-generated lower body negative pressure. METHODS: A lower body negative pressure cylinder expands and collapses longitudinally, but not radially. As the legs push footward to expand the cylinder, the air pressure in the cylinder decreases, increasing the force required to continue expanding the cylinder. In addition, valves control air flow into and out of the cylinder, and thus workload. In seven supine subjects, knee bend exercise was performed at 19 cycles per minute for 6 min. Footward force was measured with load cells, cylinder pressure with a transducer, heart rate from ECG, and oxygen consumption with turbine volumetry and gas analysis. RESULTS: Maximum footward force at the peak of the exercise cycle averaged 1120+/-88 N (114+/-9 kg), and pressure within the cylinder concomitantly decreased 26+/-3 mmHg below ambient. Heart rate and oxygen consumption increased 75+/-4 bpm and 26.3+/-1.4 ml O2/kg x min(-1) from supine resting values, respectively. CONCLUSIONS: With the air inlet valve nearly closed, exercise with this device approximates a resistance-type leg press. With more inflow of air, more rapid, aerobic knee bends can be performed. This exercise device/concept provides simultaneous dynamic musculoskeletal and cardiovascular stresses without an external power source.     

The endocrine and metabolic responses to space flight

The absence of hydrostatic forces, which results in body fluid shifts, and the absence of deformation forces on normally load-bearing tissues, appear to cause the principal disturbances found during and after space flight in the cardiovascular, fluid and electrolyte, erythropoietic, musculoskeletal, and metabolic systems. These alterations produce reduced body fluid volume, reduced musculoskeletal mass, and alterations in basal metabolism, resulting in the following consistent findings of space flight: weight loss, altered body composition, decreased orthostatic tolerance, and a compromised ability to deal with physical activity after returning from a space-flight environment. Specific changes include alterations in hydration status, resulting in a relative dehydration, loss of body calcium stores with a concomitant increase in urinary hydroxyproline, skeletal muscular atrophy, and a negative energy balance after prolonged space flight. Numerous endocrine changes have been determined during space flight, but more sensitive assay developed recently will allow careful determination of other hormone levels, and measurement of some of the primary changes that occur during the first hours of space flight. These results will be integrated into a working systems model of the physiologic response to weightlessness.     

The interactions of intensity, frequency and duration of exercise training in altering cardiorespiratory fitness

This review has grouped many studies on different populations with different protocols to show the interactive effects of intensity, frequency and duration of training as well as the effects of initial fitness levels and programme length on cardiorespiratory fitness as reflected by aerobic power (VO2max). Within each level of exercise duration, frequency, programme length or initial fitness level, the greatest improvements in aerobic power occur when the greatest challenge to aerobic power occurs i.e., when intensity is from 90 to 100% of VO2max. The pattern of improvement where different intensities are compared with different durations suggests that when exercise exceeds 35 minutes, a lower intensity of training results in the same effect as those achieved at higher intensities for shorter durations. Frequencies of as low as 2 per week can result in improvements in less fit subjects but when aerobic power exceeds 50 ml/kg/min, exercise frequency of at least 3 times per week is required. As the levels of initial fitness improve, the changes in aerobic power decreases regardless of the intensity, frequency or duration of exercise. Although these pooled data suggest that maximal gains in aerobic power are elicited with intensities between 90 to 100% VO2max, 4 times per week with exercise durations of 35 to 45 minutes, it is important to note that lower intensities still produce effective changes and reduce the risks of injury in non-athletic groups.     

Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness

This paper reviews the influence of several perturbations (physical exercise, heat stress, terrestrial altitude, microgravity, and trauma/sickness) on adaptations of blood volume (BV), erythrocyte volume (EV), and plasma volume (PV). Exercise training can induce BV expansion: PV expansion usually occurs immediately, but EV expansion takes weeks. EV and PV expansion contribute to aerobic power improvements associated with exercise training. Repeated heat exposure induces PV expansion but does not alter EV. PV expansion does not improve thermoregulation, but EV expansion improves thermoregulation during exercise in the heat. Dehydration decreases PV (and increases plasma tonicity) which elevates heat strain and reduces exercise performance. High altitude exposure causes rapid (hours) plasma loss. During initial weeks at altitude, EV is unaffected, but a gradual expansion occurs with extended acclimatization. BV adjustments contribute, but are not key, to altitude acclimatization. Microgravity decreases PV and EV which contribute to orthostatic intolerance and decreased exercise capacity in astronauts. PV decreases may result from lower set points for total body water and central venous pressure, while EV decreases may result from increased erythrocyte destruction. Trauma, renal disease, and chronic diseases cause anemia from hemorrhage and immune activation which suppresses erythropoiesis. The re-establishment of EV is associated with healing, improved life quality, and exercise capabilities for these injured/sick persons.     

Cardiovascular deconditioning during space flight and the use of saline as a countermeasure to orthostatic intolerance

Alterations in the physiology of the cardiovascular system have been noted during all exposures to the microgravity experienced in space flight. Of most importance to the operational function of Space Shuttle crewmembers is orthostatic intolerance. Although complex changes occur as a result of adaptation to weightlessness, the redistribution and loss of body fluid apparently plays a substantial role. Utilizing ground-based bed rest data as an analog to the absence of gravitational force encountered in orbital flight, a saline loading countermeasure was developed. In this study, 17 crewmembers consumed various amounts of salt and fluid prior to the reentry phase of Space Shuttle flights; 9 other astronauts served as control subjects. The countermeasure reduced the heart rate response to orthostatic stress 29% and reversed the fall in mean blood pressure. A Cardiovascular Index of Deconditioning (defined as CID = delta HR - delta SBP + delta DBP) equalled 21 in those who utilized the countermeasure, a significant improvement toward baseline (p less than 0.003) when compared to the control group CID = 49. The encouraging results of these investigations have led to the adoption of the countermeasure as an operational procedure by Shuttle crewmembers.     

Plasma catecholamine response to acute psychological stress in humans: relation to aerobic fitness and exercise training

Existing cross-sectional studies on plasma catecholamine activity provide no support for the concept that a markedly high level of aerobic fitness modifies sympathoadrenal response to an acute psychological challenge in humans. In contrast, compromised sympathetic nervous system activity has been observed in individuals with low aerobic fitness and the relationship probably reflects a global deconditioning syndrome involving both psychological and physiological processes. The relationship between low levels of fitness and plasma norepinephrine may appear as a blunted or augmented response depending upon the nature of the task. Short-term (3-4 months) exercise training studies conducted with humans have not indicated a substantial adaptation in the relative plasma catecholamine change from a preexisting baseline during exposure to acute psychological stress. Exercise training can lower basal circulating plasma norepinephrine, resulting in lower absolute concentrations during an acute challenge, but the studies in this area lack consistency and the absolute change tends to be modest. There is no evidence that fitness or exercise training is significantly associated with plasma epinephrine activity during short-term psychological stress.     

The role of exercise in the treatment of cardiovascular disease associated with type 2 diabetes mellitus

The role of exercise training in the prevention and treatment of type 2 diabetes mellitus has been studied extensively over the past two decades. Although the primary treatment aim for patients with type 2 diabetes is metabolic control, the morbidity and mortality associated with the disease is more a function of cardiovascular disease. As exercise is associated with favourable reductions in the risk for cardiovascular disease in other high-risk populations, here we explore the role of exercise in the treatment of cardiovascular maladaptations associated with type 2 diabetes.The cardiovascular adaptation to type 2 diabetes is characterised by hypertrophy, stiffening and loss of functional reserve. Clinically, the cardiovascular adaptations to the diabetic state are associated with an increased risk for cardiovascular disease. Functionally, these adaptations have been shown to contribute to a reduced exercise capacity, which may explain the reduced cardiovascular fitness observed in this population.Exercise training is associated with improved exercise capacity in various populations, including type 2 diabetes. Several structural and functional adaptations within the cardiovascular system following exercise training could explain these findings, such as reductions in ventricular and vascular structural hypertrophy and compliance coupled with increased functional reserve. Although these cardiovascular adaptations to aerobic exercise training have been well documented in older populations with similar decrements in cardiovascular fitness and function, they have yet to be examined in patients with type 2 diabetes. For this reason, we contend that exercise training may be an excellent therapeutic adjunct in the treatment of diabetic cardiovascular disease.