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.     

Lower-body negative-pressure exercise and bed-rest-mediated orthostatic intolerance

PURPOSE: Supine, moderate exercise is ineffective in maintaining orthostatic tolerance after bed rest (BR). Our purpose was to test the hypothesis that adding an orthostatic stress during exercise would maintain orthostatic function after BR. METHODS: Seven healthy men completed duplicate 15-d 6 degrees head-down tilt BR using a crossover design. During one BR, subjects did not exercise (CON). During another BR, subjects exercised for 40 min.d(-1) on a supine treadmill against 50-60 mm Hg LBNP (EX). Exercise training consisted of an interval exercise protocol of 2- to 3-min intervals alternating between 41 and 65% (.)VO(2max). Before and after BR, an LBNP tolerance test was performed in which the LBNP chamber was decompressed in 10-mm Hg stages every 3 min until presyncope. RESULTS: LBNP tolerance, as assessed by the cumulative stress index (CSI) decreased after BR in both the CON (830 +/- 144, pre-BR vs 524 +/- 56 mm Hg.min, post-BR) and the EX (949 +/- 118 pre-BR vs 560 +/- 44 mm Hg.min, post-BR) conditions. However, subtolerance (0 to -50 mm Hg LBNP) heart rates were lower and systolic blood pressures were better maintained after BR in the EX condition compared with CON. CONCLUSION: Moderate exercise performed against LBNP simulating an upright 1-g environment failed to protect orthostatic tolerance after 15 d of BR.     

Fludrocortisone does not prevent orthostatic hypotension in astronauts after spaceflight

BACKGROUND: During stand/tilt tests after spaceflight, 20% of astronauts experience orthostatic hypotension and presyncope. Spaceflight-induced hypovolemia is a contributing factor. Fludrocortisone, a synthetic mineralocorticoid, has been shown to increase plasma volume and orthostatic tolerance in Earth-bound patients. The efficacy of fludrocortisone as a treatment for postflight hypovolemia and orthostatic hypotension in astronauts has not been studied. Our purpose was to test the hypothesis that astronauts who ingest fludrocortisone prior to landing would have less loss of plasma volume and greater orthostatic tolerance than astronauts who do not ingest fludrocortisone. METHODS: There were 25 male astronauts who were randomized into 2 groups: placebo (n = 18) and fludrocortisone (n = 7), and participated in stand tests 10 d before launch and 2-4 h after landing. Subjects took either 0.3 mg fludrocortisone or placebo orally 7 h prior to landing. Supine plasma and red cell volumes, supine and standing HR, arterial pressure, aortic outflow, and plasma norepinephrine and epinephrine were measured. RESULTS: On landing day, 2 of 18 in the placebo group and 1 of 7 in the fludrocortisone group became presyncopal (chi2 = 0.015, p = 0.90). Plasma volumes were significantly decreased after flight in the placebo group, but not in the fludrocortisone group. During postflight stand tests, standing plasma norepinephrine was significantly less in the fludrocortisone group compared with the placebo group. CONCLUSIONS: Treatment with a single dose of fludrocortisone results in protection of plasma volume but no protection of orthostatic tolerance. Fludrocortisone is not recommended as a countermeasure for spaceflight-induced orthostatic intolerance.     

Maximal ventilation after exhausting exercise

It remains unclear whether the hyperpnea of exercise severely stresses the ventilatory musculature. We hypothesized that the ability to ventilate maximally is decreased during and immediately following exhausting exercise. Subjects performed isocapnic maximal voluntary ventilations (60-s MVV) before, during the final minute, and after exhausting treadmill exercise lasting either 3-10 min or 60 min. Severe exercise lasting 3-10 min failed to change the 60-s MVV. In contrast, during the final minute and 5 and 10 min after 60 min of exhausting exercise, eight non-runners showed significantly lower (P less than 0.01) 60-s MVV values in comparison to control values. Eight runners had a lower (P less than 0.05) 60-s MVV 10 min post-exercise as compared with control and exercise values. Our data suggest that the capacity to ventilate maximally declines only in long-term exhausting exercise and that this decrement in most pronounced in non-runners.     

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.     

Inspiratory resistance as a potential treatment for orthostatic intolerance and hemorrhagic shock

Loss of consciousness due to central hypovolemia can occur due to sudden cardiovascular decompensation in normal individuals or hypovolemic shock in wounded patients. A variety of devices have been developed to sustain perfusion to the brain including anti-G suits worn by pilots and returning astronauts and applied to patients as "shock trousers." However, all countermeasures developed to date suffer from problems that limit their utility in the field. An "impedance threshold device" (ITD) has recently been developed that acutely increases central blood volume by forcing the thoracic muscles to develop increased negative pressure, thus drawing venous blood from extrathoracic cavities into the heart and lungs. We review here a series of experiments that demonstrate the application of the ITD to a variety of experimental conditions, including its use to: 1) increase heart rate, stroke volume, and arterial BP in normovolemia and hypovolemia; 2) increase cerebral blood flow velocity; 3) reset cardiac baroreflex function to a higher operating range for BP; 4) lower intracranial pressure; and 5) reduce orthostatic symptoms. In this brief review, we present evidence which supports further consideration of using inspiratory resistance as a countermeasure against circulatory collapse associated with orthostatic instability and hemorrhagic shock.     

Blood pressure and plasma renin activity as predictors of orthostatic intolerance

Some physiological responses to head-up tilt and 3 h standing were evaluated in 13 dehydrated subjects. Seven of the subjects proved to be orthostatically intolerant (INT), exhibiting presyncopal symptoms. Before the symptoms manifest themselves the INT subjects had consistently lower (p less than 0.05) systolic blood pressures, generally lower diastolic and pulse pressures, and elevated (p less than 0.05) plasma renin activity (PRA) compared to the tolerant (TOL) subjects. Plasma vasopressin usually increased more in the INT subjects, but appeared to be related to the severity of presyncopal symptoms rather than to the upright posture per se. It is concluded that systolic and pulse pressures, with PRA, may allow discrimination between TOL, and potentially INT individuals; i.e., predict orthostatic intolerance. It is suggested that dehydration could provide a valuable physiological model for elucidating the causes of orthostatic intolerance.     

Aerobic fitness does not contribute to prediction of orthostatic intolerance

Several investigations have suggested that orthostatic tolerance may be inversely related to aerobic fitness (VO2max). To test this hypothesis, 18 males (age 29 to 51 yr) underwent both treadmill VO2max determination and graded lower body negative pressures (LBNP) exposure to tolerance. VO2max was measured during the last minute of a Bruce treadmill protocol. LBNP was terminated based on pre-syncopal symptoms, and LBNP tolerance (peak LBNP) was expressed as the cumulative product of LBNP and time (torr-min). Changes in heart rate, stroke volume, cardiac output, blood pressure, and impedance rheographic indices of mid-thigh-leg fluid accumulation were measured at rest and during the final minute of LBNP. For all 18 subjects, mean (+/- SE) fluid accumulation index and leg venous compliance index at peak LBNP were 139 +/- 22 ml and 3.9 +/- 0.4 ml . 100 ml . torr-min-2 x 10(3), respectively. Pearson product-moment correlations and step-wise linear regression were used to investigate relationships with peak LBNP. Variables associated with endurance training, such as VO2max and percent body fat, were not found to correlate significantly (P less than 0.05) with peak LBNP and did not add sufficiently to the prediction of peak LBNP to be included in the step-wise regression model. The step-wise regression model included only fluid accumulation index, leg venous compliance index, and blood volume, and resulted in a squared multiple correlation coefficient of 0.978. These data do not support the hypothesis that orthostatic tolerance as measured by LBNP is lower in individuals with high aerobic fitness.     

Bed rest effects on human calf hemodynamics and orthostatic intolerance: a model-based analysis

INTRODUCTION: Microgravity-induced orthostatic intolerance continues to be a primary problem after space missions. Its etiology remains uncertain despite significant research efforts over the past years. We hypothesized that calf hemodynamic parameters (compliance and resistance) are significantly affected by 14 to 16-d head-down bed rest (simulated microgravity), and their alterations play a role in the pathogenesis of orthostatic intolerance (OI) following bed rest. METHODS: To estimate these parameters, we developed a model-based approach to quantitatively simulate calf vascular response to venous occlusion, which only necessitates measurement of plethysmography data. In this study, plethysmography data were obtained from 29 subjects before and after 14-16 d of head-down bed rest. The subjects also underwent a tilt/stand test before and after bed rest. RESULTS: Statistical analyses demonstrated an increase in calf compliance (1.87 +/- 0.08, mean +/- SE, pre-bed rest; 2.16 +/- 0.10, end-bed rest) but no significant change in vascular resistance following bed rest. Compared with the tilt-intolerant subjects, those who were tilt-tolerant before bed rest had significantly higher calf compliance [2.00 +/- 0.09 (tolerant); 1.58 +/- 0.09 (intolerant)] and higher vascular resistance [7.79 +/- 0.18 (tolerant); 6.91 +/- 0.40 (intolerant)]. After bed rest, no such difference was detected. DISCUSSION: Based on these results, we validated the hypothesis that, instead of causing orthostatic intolerance, higher calf compliance before bed rest leads to recruitment of compensatory mechanisms (validated by the enhanced vascular resistance during venous occlusion) for a better toleration of orthostatic stress. With the absence of orthostatic challenge during bed rest, the difference in calf hemodynamic parameters is attenuated between the tilt-tolerant and tilt-intolerant groups.     

Effect of long-term physical exercise on lymphocyte reactivity: similarity to spaceflight reactions

The response of critical immunological parameters in seven athletes to the sustained physical stress of marathon running was assessed. Variables analysed were the responsiveness of lymphocytes (measured as mitogenic response to concanavalin A), the numbers of lymphocytes, their subsets, and leukocyte numbers. In addition, blood levels of cortisol, epinephrine, and norepinephrine were determined. After the run, lymphocyte responsiveness was severely depressed to 1-70% of the resting values, even though the lymphocyte counts did not change. Leukocyte counts were elevated 2.8-fold. No dramatic changes were found within the lymphocyte subsets, although an increase in pan T-cells and the helper/inducer subset 2 d after the run was significant. In addition, the numbers of B-cells decreased significantly. No change was observed within the suppressor/cytotoxic subset. Cortisol increased 2.1-fold, epinephrine 3.2-fold and norepinephrine 2.7-fold. All these parameters returned to baseline values within 2 d. These data were compared with data obtained during and after spaceflight. We conclude that prolonged physical stress of marathon running induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight.     

Aerobic exercise as a countermeasure for microgravity-induced bone loss and muscle atrophy in a rat hindlimb suspension model

BACKGROUND: Loss of bone and skeletal muscle atrophy resulting from non-weight-bearing are major concerns associated with microgravity environment and spaceflight deconditioning. The objective of this research was to address the fundamental issue of whether bone loss and muscle atrophy could be attenuated using weight-bearing aerobic exercise on a treadmill as a countermeasure in rats subjected to simulated weightlessness by hindlimb suspension. METHOD: Bone and muscle from control and hindlimb-suspended groups with and without exercise were evaluated by bone mineral density (BMD), mechanical tests, bone histomorphometry and muscle mass. RESULTS: Femoral BMD of hindlimb-suspended (HS) rats subjected to treadmill exercise was significantly greater than femoral BMD of HS rats without exercise and also was equivalent to that of weight-bearing controls. Muscle mass from HS rats exercised on a treadmill was significantly greater than muscle mass from HS rats that did not exercise. Exercise did not result in muscle mass equal to that of controls, however. In addition, histomorphometric analysis of the metaphysis of the proximal tibia revealed that HS rats that exercised did not maintain bone formation equivalent to controls. No other bone parameters were found to vary significantly between groups. CONCLUSIONS: It was concluded that moderate aerobic exercise on a treadmill did attenuate bone loss and muscle atrophy due to simulated weightlessness by hindlimb suspension, however its effectiveness differed by tissue, anatomical site and parameter investigated.     

立位耐力不良飞行员模拟飞行中心理生理反应与心率变异性分析

目的探讨立位耐力不良飞行员模拟空中环境下心脏自主神经功能调节状态和心理生理反应特点，为空中晕厥的诊断提供客观的评价方法。方法对２２名立位耐力不良（不良组）飞行员进行了连续动态心电记录和模拟飞行条件下的心理生理参数测定与心率变异性（ＨＲＶ）分析，并与１５名立位耐力正常的健康飞行员（健康组）做了对比。结果不良组飞行员在模拟仪表飞行中心理生理储备能力明显降低，表现为完成两项任务的质量和处理信息速度的能力较健康组低（Ｐ＜０．０１）；心血管自主神经功能严重失调；心理生理储备值与ＨＲＶ多数指标之间存在明显的相关性。结论结合模拟仪表飞行条件下的心理生理负荷评定和ＨＲＶ分析能较客观地反映立位耐力不良飞行员心血管自主神经功能障碍的发生机制和调节规律，为空中晕厥的诊断提供量化的指标。     

Plantar stimulation as a possible countermeasure to microgravity-induced neuromotor degradation

Since the early days of human spaceflight it has been reported that extended exposure to gravitational unloading results in a myriad of neuromotor adaptations that, while appropriate for microgravity, are maladaptive upon return to Earth. If not countered, these adverse effects of microgravity can result in negative health consequences and place crewmembers at risk for injury. The most commonly used countermeasures in today's space programs are those requiring active participation in prescribed exercise regimes that are time intensive, not completely effective, and have led to relatively low compliance. In this paper we review evidence that suggests a "passive" countermeasure in the form of dynamic foot stimulation (DFS) to the plantar surfaces of the feet may be a useful supplement to more traditional exercise countermeasures. This includes reports from both Russian and American investigators using both human and animal models indicating the overall effectiveness of DFS, the specific stimulation parameters involved, and a physiological explanation for the outcomes associated with the exposure to microgravity. Additionally, the use of DFS has the potential to benefit those at risk for muscle atrophy, including those experiencing extended bedrest, the elderly, and those with spinal cord injuries.     

Pulmonary function tests fail to predict exercise intolerance in sheep with emphysema

PURPOSE: The purpose of this study was to examine ventilatory parameters, gas exchange, and exercise tolerance in sheep undergoing cardiopulmonary exercise testing and pulmonary function testing at baseline and after induction of emphysema using nebulized papain, to improve our understanding of the contributions of parenchymal emphysema with minimal airway disease to exertional dysfunction in mild-to-moderate emphysema. METHODS: Static lung physiology (total lung capacity, residual volume, static elastance, and diffusing capacity of carbon monoxide) and lung (ZL) input impedance were measured, and cardiopulmonary exercise testing (CPET) was performed in 12 sheep before and after induction of emphysema. Papain treatment was delivered over a 12-wk period, as a single dose per week, to induce mild-to-moderate emphysema without airway disease. Static and dynamic lung physiology, as well as CPET, were then repeated. RESULTS: At the emphysema time point (EMPH), all animals were asymptomatic for emphysema at rest. There was a 60% increase in residual volume and a 57% decrease in static elastance, accompanied by a 36% reduction in diffusing capacity. Airway resistance was consistently, mildly increased, resulting in an increased expiratory time constant for all sheep at EMPH. There were no significant differences at EMPH versus baseline for any measured physiological variables during CPET (VO2peak, VCO2peak, RER, anaerobic threshold, O2 pulse, tidal volume, peak flow, peak VE/VO2, or peak VE). CONCLUSION: There is notable conservation of exercise capacity in sheep with mild-to-moderate parenchymal emphysema; this is not predicted by pulmonary function tests. In the absence of significant airway narrowing, mild-to-moderate emphysema is unlikely to result in airflow limitation.     

Strength training as a countermeasure to aging muscle and chronic disease

Strength training (ST) has long been considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure associated with advanced age but, until recently, the evidence was insufficient to support its role in the prevention or treatment of disease. In recent decades, there has been a long list of quality reviews examining the effects of ST on functional abilities and a few on risk factors for specific diseases, but none have provided a comprehensive assessment of ST as an intervention for a broad range of diseases. This review provides an overview of research addressing the effectiveness of ST as an intervention for the prevention or treatment of the adverse consequences of (i) aging muscle; (ii) the metabolic syndrome (MetS) and its components, i.e. insulin resistance, abdominal obesity, hyperlipidaemia and hypertension; (iii) fibromyalgia; (iv) rheumatoid arthritis; and (v) Alzheimer's disease. Collectively, these studies indicate that ST may serve as an effective countermeasure to some of the adverse consequences of the MetS, fibromyalgia and rheumatoid arthritis. Evidence in support of the hypothesis that ST reduces insulin resistance or improves insulin action comes both from indirect biomarkers, such as glycosylated haemoglobin (HbA(1c)), and insulin responses to oral glucose tolerance tests, as well as from more direct procedures such as hyperglycaemic and hyperinsulinaemic-euglycaemic clamp techniques. The evidence for the use of ST as a countermeasure of abdominal obesity is less convincing. Although some reports show statistically significant reductions in visceral fat, it is unclear if the magnitude of these changes are physiologically meaningful and if they are independent of dietary influences. The efficacy of ST as an intervention for reducing dyslipidaemia is at best inconsistent, particularly when compared with other pharmacological and non-pharmacological interventions, such as aerobic exercise training. However, there is more consistent evidence for the effectiveness of ST in reducing triglyceride levels. This finding could have clinical significance, given that elevated triglyceride is one of the five criterion measures for the diagnosis of the MetS. Small to moderate reductions in resting and exercise blood pressure have been reported with some indication that this effect may be genotype dependent. ST improves or reverses some of the adverse effects of fibromyalgia and rheumatoid arthritis, particularly pain, inflammation, muscle weakness and fatigue. Investigations are needed to determine how these effects compare with those elicited from aerobic exercise training and/or standard treatments. There is no evidence that ST can reverse any of the major biological or behavioural outcomes of Alzheimer's disease, but there is evidence that the prevalence of this disease is inversely associated with muscle mass and strength. Some indicators of cognitive function may also improve with ST. Thus, ST is an effective countermeasure for some of the adverse effects experienced by patients of many chronic diseases, as discussed in this review.     

Maximal lactate steady state as a training stimulus

The present study examined the use of the maximal lactate steady state (MLSS) as an exercise training stimulus in moderately trained runners. Fourteen healthy individuals (12 male, 2 female; age 25 +/- 6 years, height 1.76 +/- 0.05 m, body mass 76 +/- 8 kg mean +/- SD) took part in the study. Following determination of the lactate threshold (LT), VO2max, running velocity at MLSS (vMLSS) and a control period of 4 weeks, participants were pair matched and split into two cohorts performing either continuous (CONT: 2 sessions/week at vMLSS) or intermittent treadmill running (INT: 2 sessions/week, 3-min repetitions 0.5 km . h (-1) above and below vMLSS). vMLSS increased in CONT by 8 % from 12.3 +/- 1.5 to 13.4 +/- 1.6 km . h (-1) (p < 0.05) and in INT by 5 % from 12.2 +/- 1.9 km . h (-1) to 12.9 +/- 1.9 km . h (-1) (p < 0.05). Running speed at the LT increased by 7 % in the CONT group (p < 0.05) and by 9 % in the INT group (p < 0.05). VO2max increased by 10 % in the CONT group (p < 0.05) and by 6 % in INT (p < 0.05). Two sessions per week at vMLSS are capable of eliciting improvements in the physiological responses at LT, MLSS, and VO2max in moderately trained runners.