Cardiac atrophy in women following bed rest.

Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P < 0.001), and the length of the major axis of the LV (90 +/- 6 to 84 +/- 7 mm. P < 0.001), similar to what has been observed previously in men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P < 0.001) and RV masses (0.7 +/- 0.1 to 0.8 +/- 0.2 g/kg; P = 0.002), as well as mean wall thickness (9 +/- 2 to 11 +/- 1 mm; P = 0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P < 0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103 +/- 14 to 80 +/- 16 ml; P = 0.02) and major-axis length (91 +/- 5 to 88 +/- 7 mm; P = 0.003). All subjects lost an equivalent amount of body mass (3.4 +/- 0.2 kg control; 3.1 +/- 0.04 kg exercise; 2.8 +/- 0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.     

Energy and thermal regulation during bed rest and spaceflight

In planning for long-duration (1- to 2-yr) space missions (microgravity), the availability of oxygen, water, and food is critical for survival. If astronauts would consume approximately 3,100 kcal and 2.2 liters of fluid per day, the requirements for a 2-yr flight would be 2,263,000 kcal and 1,606 liters for each astronaut. These estimates, based on limited microgravity simulation and flight data, include 1 h/day of moderate isotonic exercise. Each 30-min/day reduction in exercise training time would save 110,869 kcal and 91 liters of water per year. One daily 5-h extravehicular sortie at an average work rate of 1.7 l/min would require an additional 529,250 kcal and 1,095 liters of water per year. Results from microgravity simulation (bed rest) experiments suggest that 1) there is uncertainty whether basal metabolism is unchanged, 2) submaximal ergometer exercise oxygen uptake appears to be unchanged or lower, and 3) without vigorous exercise training near peak levels, the peak oxygen uptake is definitely reduced. In addition, the equilibrium level of exercise core temperature is elevated excessively by approximately 0.5 degrees C after bed-rest acclimation. Changes in the efficiency of work or metabolism in any or all of these conditions could affect nutritional requirements for long spaceflights. Further research is necessary to elucidate the metabolic factors that would be changed and the energy cost of intra- and extravehicular activity during prolonged exposure to microgravity.     

Cardiorespiratory responses to physical work during and following 17 days of bed rest and spaceflight.

To determine the influence of a 17-day exposure to real and simulated spaceflight (SF) on cardiorespiratory function during exercise, four male crewmembers of the STS-78 space shuttle flight and eight male volunteers were studied before, during, and after the 17-day mission and 17 days of -6 degrees head-down-tilt bed rest (BR), respectively. Measurements of oxygen uptake, pulmonary ventilation, and heart rate were made during submaximal cycling 60, 30, and 15 days before the SF liftoff and 12 and 7 days before BR; on SF days 2, 8, and 13 and on BR days 2, 8, and 13; and on days 1, 4, 5, and 8 after return to Earth and on days 3 and 7 after BR. During 15 days before liftoff, day 4 after return, and day 8 after return and all BR testing, each subject completed a continuous exercise test to volitional exhaustion on a semirecumbent (SF) or supine (BR) cycle ergometer to determine the submaximal and maximal cardiorespiratory responses to exercise. The remaining days of the SF testing were limited to a workload corresponding to 85% of the peak pre-SF peak oxygen uptake (Vo2 peak) workload. Exposure to and recovery from SF and BR induced similar responses to submaximal exercise at 150 W. Vo2 peak decreased by 10.4% from pre-SF (15 days before liftoff) to day 4 after return and 6.6% from pre-BR to day 3 after return, which was partially (SF: -5.2%) or fully (BR) restored within 1 wk of recovery. Workload corresponding to 85% of the peak pre-SF Vo2 peak showed a rapid and continued decline throughout the flight (SF day 2, -6.2%; SF day 8, -9.0%), reaching a nadir of -11.3% during testing on SF day 13. During BR, Vo2 peak also showed a decline from pre-BR (BR day 2, -7.3%; BR day 8, -7.1%; BR day 13, -9.0%). These results suggest that the onset of and recovery from real and simulated microgravity-induced cardiorespiratory deconditioning is relatively rapid, and head-down-tilt BR appears to be an appropriate model of this effect, both during and after SF.     

Lung function during and after prolonged head-down bed rest.

We determined the effects of prolonged head-down tilt bed rest (HDT) on lung mechanics and gas exchange. Six subjects were studied in supine and upright postures before (control), during [day 113 (D113)], and after (R + number of days of recovery) 120 days of HDT. Peak expiratory flow (PF) never differed between positions at any time and never differed from controls. Maximal midexpiratory flow (FEF(25-75%)) was lower in the supine than in the upright posture before HDT and was reduced in the supine posture by about 20% between baseline and D113, R + 0, and R + 3. The diffusing capacity for carbon monoxide corrected to a standardized alveolar volume (volume-corrected DL(CO)) was lower in the upright than in the supine posture and decreased in both postures by 20% between baseline and R + 0 and by 15% between baseline and R + 15. Pulmonary blood flow (Q(C)) increased from R + 0 to R + 3 by 20 (supine) and 35% (upright). As PF is mostly effort dependent, our data speak against major respiratory muscle deconditioning after 120 days of HDT. The decrease in FEF(25-75%) suggests a reduction in elastic recoil. Time courses of volume-corrected DL(CO) and Q(C) could be explained by a decrease in central blood volume during and immediately after HDT.     

Visual function after prolonged bed rest

The present study evaluated the claim of earlier reports, that of bed rest-induced alterations in visual function. Indices of visual function were studied in 10 healthy male subjects, during 35 days of horizontal bed rest. Before and after the 35 day bed rest, both eyes of all subjects were examined for visual acuity, intraocular pressure, contrast sensitivity, stereopsis and visual field. Pre- and post-bed rest values were compared with Student's T-test. There were no significant differences in any of the measured indices of visual function.     

Muscle atrophy and hormonal regulation in women in 120 day bed rest

It is known, that exposures to real and simulated weightlessness results in pronounced reduction of the cross-sectional area (CSA) of slow-twitch(ST) and fast-twitch(FT) fibers of mammalian muscle. After space flights of various durations, head-down tilt bedrest, and 7-days of dry immersion sufficient [correction of isufficient] reductions of CSA of both fiber types were observed in man and in the majority of these cases the atrophy levels of ST and FT fibers were similar. It is well-known, that elevated contractile activities of muscle system attenuate muscle atrophy development. It remains still unclear which fiber type is more susceptible to training effects. Among physiological mechanisms involved in the process of microgravity-induced atrophy development which are supposed to be the most important are the profound decrease of a mechanical tension of muscle fibers in situ and alterations in hormonal control of muscle protein metabolism. But it is not known yet if the hormonal changes in the course of exposure to gravitational unloading match somehow the time-course of muscle fiber size reduction. The aim of the study was to investigate the time-course of muscle fiber atrophy development and changes in plasma hormone levels in the course of long-duration BR with and without high-intensity locomotor interval physical training.     

Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function.

We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.     

Sympathetic discharge and vascular resistance after bed rest

Shoemaker, J. Kevin, Cynthia S. Hogeman, Urs A. Leuenberger,Michael D. Herr, Kristen Gray, David H. Silber, and Lawrence I. Sinoway. Sympathetic discharge and vascular resistance after bedrest. J. Appl. Physiol. 84(2):612-617, 1998.The effect of 6° head-down-tilt bedrest (HDBR) for 14 days on supine sympathetic discharge andcardiovascular hemodynamics at rest was assessed. Mean arterialpressure, heart rate (n = 25), musclesympathetic nerve activity (MSNA; n = 16) burst frequency, and forearm blood flow(n = 14) were measured, and forearmvascular resistance (FVR) was calculated. Stroke distance,our index of stroke volume, was derived from measurements of aorticmean blood velocity (Doppler) and R-R interval(n = 7). With these data, an index oftotal peripheral resistance was determined. Heart rate at rest wasgreater in the post (71 ± 2 beats/min)- compared with the pre-HDBRtest (66 ± 2 beats/min; P < 0.003), but mean arterial pressure was unchanged. Aortic strokedistance during post-HDBR (15.5 ± 1.1 cm/beat) was reduced frompre-HDBR levels (20.0 ± 1.5 cm/beat)(P < 0.03). Also, MSNA burstfrequency was reduced in the post (16.7 ± 2.8 beats/min)- comparedwith the pre (25.2 ± 2.6 beats/min)-HDBR condition(P < 0.01). Bed rest did not alterforearm blood flow, FVR, or total peripheral resistance. Thusreductions in MSNA with HDBR were not associated with a decrease inFVR.

     

Maximal instantaneous muscular power after prolonged bed rest in humans.

A reduction in lower limb cross-sectional area (CSA) occurs after bed rest (BR). This should lead to an equivalent reduction in maximal instantaneous muscular power (W(p)) if the body segments' lengths remain unchanged. W(p) was determined during maximal jumps off both feet on a force platform before and on days 2, 6, 10, 32, and 48 after a 42-day duration BR. CSA of thigh muscles was measured by magnetic resonance imaging before and on day 5 after BR. Before BR, W(p) was 3.63 +/- 0.43 kW or 48.6 +/- 3.3 W/kg. On days 2 and 6 after BR, W(p) was reduced by 23.7 +/- 6.9 and 22.7 +/- 5.4% (P < 0.01), respectively. Thigh extensors CSA (CSAEXT) was 16.7 +/- 4.7% (P < 0.01) lower than before. When normalized per CSAEXT, W(p) was reduced by only 4.8 +/- 4.5% (P < 0.05). By day 48 of recovery, W(p) had returned to baseline values. Therefore, if W(p) is appropriately normalized for CSA of the extensor muscles, the reduction in CSAEXT explains most of the decrease in W(p) decrease after BR. Other factors such as a deficit in neural activation or a decrease in fiber-specific tension may account for only 5% of the W(p) loss after BR.     

Maximal and submaximal forces of slow fibers in human soleus after bed rest.

The effects of 2 and 4 mo of bed rest, with or without exercise countermeasures, on the contractile properties of slow fibers in the human soleus muscle were examined. Mean fiber diameters were 8 and 36% smaller after 2 and 4 mo of bed rest, respectively, than the pre-bed rest level. Maximum tetanic force (P(o)), maximum activated force (F(max)) per cross-sectional area (CSA), and the common-logarithm value of free Ca(2+) concentration required for half-maximal activation (pCa(50)) also decreased after 2 and 4 mo of bed rest. In contrast, maximum unloaded shortening velocity (V(o)) was increased after 2 and 4 mo of bed rest. After 1 mo of recovery, fiber diameters, P(o), F(max) per CSA (P > 0.05), and pCa(50) were increased and V(o) decreased toward pre-bed rest levels. Effects of knee extension/flexion exercise by wearing an anti-G Penguin suit for 10 h daily, and the effects of loading or unloading of the plantar flexors with (Penguin-1) or without (Penguin-2) placing the elastic loading elements of the suit, respectively, were investigated during ~2 mo of bed rest. In the Penguin-1 group, mean fiber diameter, P(o), F(max) per CSA, V(o), and pCa(50) were similar before and after bed rest. However, the responses of fiber size and contractile properties to bed rest were not prevented in the Penguin-2 group, although the degree of the changes was less than those induced by bed rest without any countermeasure. These results indicate that long-term bed rest results in reductions of fiber size, force-generation capacity, and Ca(2+) sensitivity, and enhancement of shortening velocity in slow fibers of the soleus. The data indicate that continuous mechanical loading on muscle, such as stretching of muscle, is an effective countermeasure for the prevention of muscular adaptations to gravitational unloading.     

Attenuated thermoregulatory sweating and cutaneous vasodilation after 14-day bed rest in humans.

We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 h with a water-perfused blanket through which hot water (42 degrees C) was circulated. The experimental room was air-conditioned (27 degrees C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf), and tympanic temperature. We also measured sweat rate by the ventilated capsule method in which the skin area for measurement was drained by dry air conditioned at 27 degrees C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31 degrees C at the chest and 0.32 degrees C at the forearm, whereas it reduced sensitivity by 40% at the chest and 31% at the forearm. HDBR increased the threshold temperature for cutaneous vasodilation, whereas it decreased sensitivity. HDBR reduced plasma volume by 11%, whereas it did not change plasma osmolarity. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes, whereas it decreased their sensitivity by different magnitudes.     

21 Days head-down bed rest induces weakening of cell-mediated immunity - Some spaceflight findings confirmed in a ground-based analog

Several studies indicate a weakening of cell-mediated immunity (CMI) and reactivation of latent herpes viruses during spaceflight. We tested the hypothesis that head-down bed rest (HDBR), a ground-based analog of spaceflight, mimics the impact of microgravity on human immunity. Seven healthy young males underwent two periods of 3 weeks HDBR in the test facility of the German Aerospace Center. As a nutritional countermeasure aimed against bone demineralisation, 90 mmol potassium bicarbonate (KHCO(3)) was administered daily in a crossover design. Blood samples were drawn on five occasions. Whole blood was stimulated with antigen i.e. Candida albicans, purified protein derivative (PPD) tuberculin, tetanus toxoid and Cytomegalovirus (CMV) (CMV-QuantiFERON). Flow cytometric analysis included CD4(+)CD25(+)CD127(-)FOXP3(+) regulatory T cells (Tregs), γδ T cells, B cells, NK cells and dendritic cells. In one of the two bed rest periods, we observed a significant decrease in production of interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following phytohemagglutinin (PHA) stimulation, with a rapid normalization being observed after HDBR. The cytokine levels showed a V-shaped pattern that led to a relativeTh2-shift in cytokine balance. Only three individuals responded to the specific T cell antigens without showing signs of an altered response during HDBR, nor did we observe reactivation of CMV or Epstein-Barr virus (EBV). Of unknown significance, dietary supplementation with KHCO(3) counteracted the decrease in IL-2 levels during HDBR, while there was no impact on other immunological parameters. We conclude that discrete alterations in CMI may be induced by HDBR in selected individuals.     

Attenuated sympathetic nerve responses after 24 hours of bed rest

Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.     

Regulation of muscle sympathetic nerve activity after bed rest deconditioning

Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.     

Gender differences in muscle strength after 20 days bed rest

In the previous studies, when Bed rest (BR) was prolonged over 2 weeks, muscle mass and strength began progressively to become reduced. There are many publications investigating the changes in skeletal muscles during inactivity. However it is still unclear whether the changing degrees of muscle mass and strength not only in antigravity muscles but also in non-antigravity muscles differ between males and females. So, the purpose of this study is to investigate gender difference in the effect of 20 days of BR (BR 20) on regional muscle mass and strength of the arm and leg.     

Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest.

Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR), may be responsible for elevated intestinal temperature (T(in)) during exercise after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head-down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C). Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs. 96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs. 37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C-1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed. The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a centrally mediated elevation in the thermoregulatory set point during bed rest exposure.     

Calcium metabolism and cardiovascular function after spaceflight.

To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P < 0.001), elevated parathyroid hormone levels (P < 0.001), reduced calcitonin levels (P < 0.05), unchanged 1,25(OH)(2)D(3) levels, and elevated skull (P < 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P < 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals (P = 0.057). However, mean arterial pressure was elevated (P < 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism (P < 0.001), as well as BP (P < 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets (P < 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.