Atropine unmasks bed-rest effect: a spectral analysis of cardiac interbeat intervals

Bed-rest deconditioning is suspected to reduce cardiac reserve, possibly by impairing autonomic function. Heart rate response in normal subjects reveals considerable variability, reflected by a relatively broadband interbeat interval power spectrum. A reduction in this autonomically modulated variability would be predicted to cause a narrowing of the spectrum. We retrospectively analyzed data from 10 aerobically conditioned men (age range 35-49 yr) who had undergone orthostatic tolerance testing with lower body negative pressure pre-bed rest and after 7-10 days of bed rest, while on placebo and after intravenous atropine. Spectra were derived by Fourier analysis of 128 interbeat interval data sets. Spectral power was estimated by computing the root-mean-square (rms) values (mean +/- SD) for the band encompassing the 2nd to 64th harmonics from subjects with a sufficient number of beats: placebo rms is 93 +/- 33 ms for pre-bed rest and 84 +/- 38 ms for bed rest (NS, n = 6); atropine rms is 63 +/- 24 ms for pre-bed rest and 40 +/- 23 ms for bed rest (P less than 0.01; n = 7). These data suggest that atropine "unmasks" a deconditioning effect of bed rest in athletic men, evidenced by a reduction in interbeat interval spectral power not apparent with placebo. Spectral analysis offers a useful means of quantitating the effects of bed-rest deconditioning and autonomic perturbations on cardiac dynamics.     

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans.

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.     

Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration

Adaptation to spaceflight or head-down-tilt bed rest leads to hypovolemia and an apparent abnormality of baroreflex regulation of cardiac period. In a previous study, we demonstrated that both chronic (2 wk) head-down-tilt bed rest and acute induced hypovolemia led to similar impairments in spontaneous baroreflex control of cardiac period, suggesting that a reduction in plasma volume may be responsible for this abnormality after bed rest. Therefore we hypothesized that this reduced "baroreflex function" could be restored by intravenous volume infusion equivalent to the reduction in plasma volume after bed rest. Six healthy subjects underwent 2 wk of -6 degrees head-down bed rest. Beat-by-beat arterial blood pressure and ECG were recorded during 6 min of spontaneous respiration and fixed-rate breathing (0.2 Hz), and transfer function analysis between systolic blood pressure and R-R interval was performed. Plasma volume was measured with Evans blue dye, and cardiac filling pressures were directly measured (Swan-Ganz catheter). After bed rest, studies were repeated before and after plasma volume restoration, with which both plasma volume and left ventricular end-diastolic pressure were restored to pre-bed rest levels by intravenous dextran40 infusion (288 +/- 31 ml). Transfer function gain in the high-frequency range, used as an index of vagally mediated arterial-cardiac baroreflex function, decreased significantly (13.4 +/- 3.1 to 8.1 +/- 2.9 ms/mmHg, P < 0.05) after bed rest. However, reduced transfer function gain was normalized to the pre-bed rest level (12.2 +/- 3.6 ms/mmHg) after precise plasma volume restoration. This result confirms that reductions in plasma volume, rather than a unique autonomic nervous system adaptation to bed rest, are largely responsible for the observed changes in spontaneous arterial-cardiac baroreflex function after bed rest.     

卧床前后压力感受性反射机能变化的研究

许多数据表明长期失重以后立位耐力降低可能与压力感受性反射功能的改变有关。本文比较了两组被试者15天低动力卧床前后的立位耐力。以血压调节模型为基础分析了两种不同方式卧床前后单纯立位和下身负压加立位时压力感受性反射功能的改变,并用颈部加压及下身负压对中枢调节功能改变进行了观察。结果表明严格的头低位卧床后,立位耐力下降及压力感受性反射功能改变明显大于半日平卧半日倚坐者。而压力感受性反射功能的改变,特别是中枢神经系统调节功能的紊乱,是卧床后立位耐力降低的主要原因。从这种考虑为基础,作者提出了改变失重或模拟失重状态下的血液分布,调整对压力感受器的刺激,可能是预防心血管失调的有效方法。     

Effects of 17 days bed rest on the maximal isometric torque of the flexors and extensors of the ankle

Researchers examined the extent to which short-term bed rest affects maximal isometric force produced by the plantar and dorsal flexors of the ankle. Results indicate an increase in average values of maximal isometric torque throughout the study, a significant increase in isometric EMG between control and bed rest subjects, and a significant isometric EMG augmentation in bed rest subjects by the end of the study. The effects of training on maximal isometric torque and muscle function impairment are discussed.     

Influence of active recovery following prolonged bed rest on static exercise pressor response

The present study investigated the effect of active recovery, following 35 days of horizontal bed rest, on the magnitude and time course of the pressor and heart rate responses to sustained 90 minute submaximal isometric contraction of unilateral knee extensor muscles. Ten healthy male subjects were tested immediately post bed rest (Post BR) and again after 4 weeks of active recovery (Recovery). In both trials subjects sustained an absolute force equal to 30% of Post BR maximal voluntary contraction (MVC). Beat-to-beat heart rate (HR) and mean arterial blood pressure (MAP) were monitored continuously during sustained contraction using the volume-clamp technique. Despite a 24% increase in MVC, there were no significant differences in the magnitudes of HR and MAP responses between Post BR and Recovery trials, suggesting a bed rest-induced attenuation of the static exercise pressor response.     

Impaired Orthostatic Response in Patients With Type 2 Diabetes Mellitus After 48 Hours of Bed Rest

ObjectiveTo compare the effect of bed rest on orthostatic responses of patients with type 2 diabetes mellitus and nondiabetic control subjects.MethodsSix patients with type 2 diabetes and 6 nondiabetic control subjects underwent 48 hours of bed rest and 48 hours of ambulatory activity in randomized order. A 10-minute tilt test was conducted before and after each period of hospitalization, and cardiovascular responses to 80° head-up tilt were analyzed with use of a 2-factorial (study group and bed rest condition) analysis of variance design. We hypothesized that patients with diabetes would experience more severe changes in orthostatic response after bed rest.ResultsNo significant differences in orthostatic responses were observed before bed rest between control subjects and patients with diabetes. After bed rest, control subjects had a greater (P = .01) increase in heart rate during tilt in comparison with before bed rest (before versus after bed rest, 9 ± 4 versus 24 ± 7 beats/min) and maintained their blood pressure during tilt. After bed rest, patients with diabetes did not have a compensatory increase in heart rate and had a greater (P = .02) decline in systolic blood pressure during tilt in comparison with before bed rest (before versus after bed rest, -7 ± 10 versus -21 ± 11 mm Hg). Their arm and leg skin vasomotor responses (laser Doppler flowmetry) during tilt were not altered after bed rest and were similar to those in control subjects before and after bed rest.ConclusionCardiac neuropathy in patients with type 2 diabetes may prevent a compensatory heart rate response after bed rest deconditioning and result in a more severe orthostatic response. A greater decrease in blood pressure with upright tilt is evident after a relatively short period of bed rest. (Endocr Pract. 2009;15:104-110)     

Influence of simulated microgravity on human skeletal muscle architecture and function

Ten male volunteers underwent a period of prolonged bed rest. Four subjects performed exercise countermeasures 2-3 times per week, while 6 subjects received no countermeasures. After bed rest plantarflexor force declined significantly (P < 0.001) in both exercise (-42%) and control (-55%) groups. The internal architecture of the gastrocnemius medialis (GM) muscle was significantly altered. This was associated with a reduction in fascicle shortening during isometric contraction. Exercise countermeasures partially mitigated the loss of muscle force and function following 90 days of bed rest.     

Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension

We studied vagally mediated carotid baroreceptor-cardiac reflexes in 11 healthy men before, during, and after 30 days of 6 degrees head-down bed rest to test the hypothesis that baroreflex malfunction contributes to orthostatic hypotension in this model of simulated microgravity. Sigmoidal baroreflex response relationships were provoked with ramped neck pressure-suction sequences comprising pressure elevations to 40 mmHg followed by serial R-wave-triggered 15-mmHg reductions to -65 mmHg. Each R-R interval was plotted as a function of systolic pressure minus the neck chamber pressure applied during the interval. Compared with control measurements, base-line R-R intervals and the minimum, maximum, range, and maximum slope of the R-R interval-carotid pressure relationships were reduced (P less than 0.05) from bed rest day 12 through recovery day 5. Baroreflex slopes were reduced more in four subjects who fainted during standing after bed rest than in six subjects who did not faint (-1.8 +/- 0.7 vs. -0.3 +/- 0.3 ms/mmHg, P less than 0.05). There was a significant linear correlation (r = 0.70, P less than 0.05) between changes of baroreflex slopes from before bed rest to bed rest day 25 and changes of systolic blood pressure during standing after bed rest. Although plasma volume declined by approximately 15% (P less than 0.05), there was no significant correlation between reductions of plasma volume and changes of baroreflex responses. There were no significant changes of before and after plasma norepinephrine or epinephrine levels before and after bed rest during supine rest or sitting.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the moderate exercise on performance in upper/lower limb during long term bed rest

The purpose of this study was to investigate that considers the influence of the moderate exercise has on the upper limbs and the legs during 21 days head down bed rest. Therefore motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in lower leg muscles of four healthy subjects were investigated before/after and during bed rest. There were no significant differences statistically between soleus MEPs before and after bed rest in all subjects. However there were decreased tendancy in MEPs during non-exercise group. And then there were not change discriminal ability on differential threshold of weight sensory in scale test in all subjects during head down bed rest. Theses results indicate that the assign cognitive performance, sensory in scale for upper limb no changes during and after head down bed rest.     

Artificial gravity as a multi-system countermeasure: effects on cognitive function

The Space Flight Cognitive Assessment Tool for Windows (WinSCAT) is used on the International Space Station to evaluate cognitive functioning after physical insult or trauma. The current study uses WinSCAT to assess cognitive functioning in a space flight analog (bed rest) environment where intermittent artificial gravity (AG) is being tested as a countermeasure. Fifteen male subjects (8 treatment, 7 control), who participated in 21 days of 6 degree head-down tilt bed rest, were assessed during the acclimatization phase, bed rest phase, and recovery phase. Individual differences were found within both the treatment and control groups. The treatment group accounted for more off-nominal WinSCAT scores than the control group. The length of time spent in bed rest was not associated with a change in cognitive function. Individual differences in underlying cognitive ability and motivation level are other possible explanations for the current findings.     

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.     

Effect of prolonged bed rest on lung volume in normal individuals

Pulmonary function was assessed in supine subjects before, during, and after three separate bed-rest studies of 11 and 12 days duration. Forced vital capacity (FVC) increased during bed rest in each subject. Total lung capacity (TLC) was measured by helium dilution in one bed-rest study and increased in each subject, while residual volume and functional residual capacity of the respiratory system did not change. No change in FVC was found in an ambulatory control group using identical measurement techniques. Maintaining base-line plasma volume during one bed rest by the use of exogenous estrogen did not prevent an increase in FVC, and decreasing plasma volume with diuretics in ambulatory subjects to the same degree as seen in the bed rests did not cause an increase in FVC. We conclude that prolonged bed rest results in a small significant increase in TLC and that this change is not dependent on alterations in plasma volume.     

Resistance training affects GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest.

This study assessed the effects of inactivity on GLUT-4 content of human skeletal muscle and evaluated resistance training as a countermeasure to inactivity-related changes in GLUT-4 content in skeletal muscle. Nine young men participated in the study. For 19 days, four control subjects remained in a -6 degrees head-down tilt at all times throughout bed rest, except for showering every other day. Five training group subjects also remained at bed rest, except during resistance training once in the morning. The resistance training consisted of 30 isometric maximal voluntary contractions for 3 s each; leg-press exercise was used to recruit the extensor muscles of the ankle, knee, and hip. Pauses (3 s) were allowed between bouts of maximal contraction. Muscle biopsy samples were obtained from the lateral aspect of vastus lateralis (VL) muscle before and after the bed rest. GLUT-4 content in VL muscle of the control group was significantly decreased after bed rest (473 +/- 48 vs. 398 +/- 66 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively), whereas GLUT-4 significantly increased in the training group with bed rest (510 +/- 158 vs. 663 +/- 189 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively). The present study demonstrated that GLUT-4 in VL muscle decreased by approximately 16% after 19 days of bed rest, and isometric resistance training during bed rest induced a 30% increase above the value of GLUT-4 before bed rest.     

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.     

Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle

The aim was to test the hypothesis that 7 days of bed rest reduces mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after bed rest. Twelve young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from six of the subjects prior to, immediately after, and 3 h after 45 min of one-legged knee extensor exercise performed before and after bed rest. Maximal oxygen uptake decreased by 4%, and exercise endurance decreased nonsignificantly, by 11%, by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content ～45%, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activity ～8%, and miR-1 and miR-133a content ～10%. However, cytochrome c and vascular endothelial growth factor (VEGF) protein content as well as capillarization did not change significantly with bed rest. Acute exercise increased AMP-activated protein kinase phosphorylation, peroxisome proliferator activated receptor-γ coactivator-1α, and VEGF mRNA content in skeletal muscle before bed rest, but the responses were abolished after bed rest. The present findings indicate that only 7 days of physical inactivity reduces skeletal muscle metabolic capacity as well as abolishes exercise-induced adaptive gene responses, likely reflecting an interference with the ability of skeletal muscle to adapt to exercise.     

Effects of 18 days of bed rest on leg and arm venous properties.

Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100 ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure x time), decreased in all subjects after bed rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.     

An Exploratory Analysis of the Utility of Adding Cardiorespiratory Biofeedback in the Standard Care of Pregnancy-Induced Hypertension

This study examined the efficacy of a cardiorespiratory biofeedback intervention compared to bed rest in the treatment of 47 women diagnosed with pregnancy-induced hypertension (PIH). The investigation consisted of a historical control group with 31 PIH subjects receiving treatment as usual (TAU), bed rest and antihypertensive medications, and an experimental group with 16 PIH subjects receiving TAU and instruction on using a portable respiratory sinus arrhythmia (RSA) biofeedback device once daily until delivery. Results indicated that systolic and diastolic blood pressure levels were unchanged for either group. Failing to find the intended main effects, a series of exploratory analyses were performed. Findings of associated hypotheses revealed that the RSA BF group had a 35 % higher birth weight than the TAU group. The gestational age at delivery was 10 % greater in the RSA BF group than in the TAU group. A significant relationship was found between the StressEraser Total and the 1-min Apgar score. Eighty-one percent of the subjects stated that the device was relaxing. Fifty percent of the subjects believed that the device helped them fall asleep. Overall, these results suggest that portable RSA biofeedback may be effective in reducing stress during pregnancy and improving perinatal outcomes.     

Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest

To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), six healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an oral glucose tolerance test (OGTT) and a one-legged knee extensor exercise bout [45 min at 60% maximal load (W(max))] with muscle biopsies obtained from vastus lateralis before, immediately after exercise, and at 3 h of recovery. Blood samples were taken from the femoral vein and artery before and after 40 min of exercise. Glucose intake elicited a larger (P ≤ 0.05) insulin response after bed rest than before, indicating glucose intolerance. There were no differences in lactate release/uptake across the exercising muscle before and after bed rest, but glucose uptake after 40 min of exercise was larger (P ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased (P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced (P ≤ 0.05) dephosphorylation of PDH-E1α on Ser2?3, Ser2?? and Ser3??, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.     

Simulated microgravity [bed rest] has little influence on taste,odor or trigeminal sensitivity

Anecdotal evidence suggests that astronauts' perceptions of foods in space flight may differ from their perceptions of the same foods on Earth. Fluid shifts toward the head experienced in space may alter the astronauts' sensitivity to odors and tastes, producing altered perceptions. Our objective was to determine whether head-down bed rest, which produces similar fluid shifts, would produce changes in sensitivity to taste, odor or trigeminal sensations. Six subjects were tested three times prior to bed rest, three times during bed rest and two times after bed rest to determine their threshold sensitivity to the odors isoamylbutyrate and menthone, the tastants sucrose, sodium chloride, citric acid, quinine and monosodium glutamate, and to capsaicin. Thresholds were measured using a modified staircase procedure. Self-reported congestion was also recorded at each test time. Thresholds for monosodium glutamate where slightly higher during bed rest. None of the other thresholds were altered by bed rest.