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12 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids

Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 microg. kg(-1). h(-1)) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 microg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline (n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 micromol/kg) constant infusion (0.05 micromol. kg(-1). min(-1)) of l-[ring-(2)H(5)]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 +/- 2.1 (C + AA) vs. 9.0 +/- 1.0 microg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

Clinical Trial↗
NASA NTRS2002

Obstructive apnea during sleep is associated with peripheral vasoconstriction

Obstructive apnea during sleep is associated with a substantial transient blood pressure elevation. The mechanism of this pressor response is unclear. In this study we measured muscle sympathetic nerve activity (MSNA), mean arterial pressure (Psa), and mean limb blood velocity as an index of blood flow (MBV, Doppler) and calculated changes in limb vascular resistance during and after apneas during both wakefulness and sleep in patients with the obstructive sleep apnea syndrome. Immediately postapnea during sleep Psa increased significantly compared with the earlier stages of apnea and this was preceded by a rise of MSNA (n = 5). In contrast to blood pressure, MBV remained unchanged. Because resistance = blood pressure/blood flow, limb vascular resistance increased by 29 +/- 8% from late apnea to postapnea (n = 7, p < 0.002). Voluntary breathhold maneuvers during room air exposure evoked similar responses (n = 10). Supplemental oxygen administered via nonrebreather face mask attenuated the MSNA and vasoconstrictor responses to obstructive (n = 2) and voluntary apneas (n = 10). Our data suggest that obstructive apneas in patients with the obstructive apnea syndrome are accompanied by transient limb vasoconstriction. This vasoconstrictor response appears to be, at least in part, mediated by the sympathetic nervous system and may be linked to hypoxia.

NASA Discipline Cardiopulmonary↗
NASA NTRS1998

Insight into mechanisms of reduced orthostatic performance after exposure to microgravity: comparison of ground-based and space flight data

Since the beginning of human spaceflight, the value of understanding mechanisms of physiological adaptation to microgravity became apparent to life scientists who were interested in maintining crew health and developing countermeasures agains adverse effects of the mission. However, several characteristics associated the the logistics of spaceflight presented significant limitations to the scientific study of human adaptation to microgravity. Because space missions are so infrequent and involve minimal numbers of crewmembers, meaninful statistical analysis of data are limited. Reproducibility of results from spaceflight experiments is difficult to assess since there are few repeated space missions involving the same crewmembers. Since the emphasis of space missions is placed on operations, experiments are compromised without adequate control over various factors (e.g., time, diet, physical activities, etc.) that can impact measured responses. With the mimimal opportunity to collect spaceflight data, there is a high risk of experiments that simultaneously interfere with other experiments by the increasing demand on the crewmembers to participate in mumerous experiments proposed by multiple investigators. The technology and ability to measure physiological functions necessary to test specific hypotheses can be severely limited by physical space and power constraints of the space enviroment. Finally, technical and logistical aspects of space missions such as launch delays, extended missions, and inflight operational emergencies can significantly compromise the timing and control of experiments. These limitations have stimulated scientists to develop ground-based analogs of microgravity in an effort to investigate the effects of spaceflight on physiological function in a controlled experimental setting. The purpose of this paper is to provide a selected comparison of data collected from ground-based experiments with those obtained from spaceflight in an effort to assess the adequacy of ground analogs of actual flight for the study of human physiological adaptation to microgravity. Specifically, results from ground and spaceflight will be used to provide insight into mechanisms underlying adaptations of blood pressure regulation and reduced orthostatic performance to the microgravity environment.

Non-NASA Center↗
NASA NTRS1997

Effects of a gravity gradient on human cardiovascular responses

Eight subjects participated in one control and three rotation trials on a short-arm centrifuge such that the Gz levels at the feet were 0.5, 1.0, and 1.5 G. Trials consisted of 30 minutes of supine rest, 1 hour of rotation (or in the control, 30 additional minutes of rest and 30 minutes of standing), and a final 30-minute rest period. Measurements of heart rate, calf impedance, calf volume, and blood pressure support the findings that the highest G level is similar to standing and that the lower G levels fail to produce significant effects.

NASA Discipline Cardiopulmonary↗
NASA NTRS2001

Effects of spaceflight on human calf hemodynamics

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.

NASA Experiment Number 178294 2/2↗
NASA NTRS2001

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

Non-NASA Center↗
NASA NTRS1998

Cardiovascular function following reduced aerobic activity

PURPOSE: The aim of this study was to test the hypothesis that a sustained reduction of physical activity (deconditioning) would alter the cardiovascular regulatory function. METHODS: Nineteen young, healthy volunteers participated in physical deconditioning for a period of 8 wk. Before (pre) and following (post) physical deconditioning, the responses of heart rate (HR), mean arterial pressure (MAP, measured by Finapres), central venous pressure (CVP), stroke volume (SV, Doppler), and forearm blood flow (FBF, plethysmography) were determined during lower body negative pressure (LBNP). The carotid baroreflex (CBR) function was assessed using a train of pulsatile neck pressure (NP) and suction, and the aortic baroreflex control of HR was assessed during steady-state phenylephrine (PE) infusion superimposed by LBNP and NP to counteract the PE increased CVP and carotid sinus pressure, respectively. RESULTS: Active physical deconditioning significantly decreased maximal oxygen uptake (-7%) and LBNP tolerance (-13%) without a change in baseline hemodynamics. Plasma volume (-3% at P = 0.135), determined by Evans Blue dilution, and blood volume (-4% at P = 0.107) were not significantly altered. During LBNP -20 to -50 torr, there was a significantly greater drop of SV per unit decrease in CVP in the post- (14.7 +/- 1.6%/mm Hg) than predeconditioning (11.2 +/- 0.7%/mm Hg) test accompanied by a greater tachycardia. Deconditioning increased the aortic baroreflex sensitivity (pre vs post: -0.61 +/- 0.12 vs -0.84 +/- 0.14 bpm.mm-1 Hg, P = 0.009) and the slope of forearm vascular resistance (calculated from [MAP-CVP]/FBF) to CVP (-2.75 +/- 0.26 vs -4.94 +/- 0.97 PRU/mm Hg, P = 0.086). However, neither the CBR-HR (-0.28 +/- 0.03 VS -0.39 +/- 0.10 bpm.mm-1 Hg) nor the CBR-MAP (-0.37 +/- 0.16 vs -0.25 +/- 0.07 mm Hg/mm Hg) gains were statistically different between pre- and postdeconditioning. CONCLUSIONS: We concluded that the functional modification of the cardiac pressure-volume relationship resulted in the reduced LBNP tolerance, despite the accentuated aortic and cardiopulmonary baroreflex function following deconditioning.

Non-NASA Center↗
NASA NTRS1997

Evidence for increased beta-adrenoreceptor responsiveness induced by 14 days of simulated microgravity in humans

We studied hemodynamic responses to alpha- and beta-receptor agonists in eight healthy men before and after 14 days of 6 degrees head-down tilt (HDT) to test the hypothesis that increased adrenoreceptor responsiveness is induced by prolonged exposure to simulated microgravity. Steady-state infusions of isoproterenol (Iso) at rates of 0.005, 0.01, and 0.02 microgram.kg-1.min-1 were used to assess beta 1- and beta 2-adrenoreceptor responsiveness. Infusions of phenylephrine (PE) at rates of 0.25, 0.50, and 1.00 microgram.kg-1.min-1 were used to assess responsiveness of alpha 1-vascular adrenoreceptors. Slopes calculated from linear regressions between Iso and PE doses and changes in beat-to-beat heart rate, blood pressure, and leg vascular resistance (occlusion plethysmography) for each subject were used as an index of alpha- and beta-adrenoreceptor responsiveness. HDT increased the slopes of heart rate (1,056 +/- 107 to 1,553 +/- 83 beats micrograms-1.kg-1.min-1; P = 0.014) and vasodilation (-469 +/- 111 to -1,446 +/- 309 peripheral resistance units.microgram-1.kg-1.min-1; P = 0.0224) to Iso infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that simulated microgravity causes selective increases in beta 1- and beta 2-adrenoreceptor responsiveness without affecting alpha 1-vascular adrenoreceptor responses.

NASA Discipline Cardiopulmonary↗
NASA NTRS1997

Intramuscular deoxygenation during exercise in patients who have chronic anterior compartment syndrome of the leg

Currently, the definitive diagnosis of chronic compartment syndrome is based on invasive measurements of intracompartmental pressure. We measured the intramuscular pressure and the relative oxygenation in the anterior compartment of the leg in eighteen patients who were suspected of having chronic compartment syndrome as well as in ten control subjects before, during, and after exercise. Chronic compartment syndrome was considered to be present if the intramuscular pressure was at least fifteen millimeters of mercury (2.00 kilopascals) before exercise, at least thirty millimeters of mercury (4.00 kilopascals) one minute after exercise, or at least twenty millimeters of mercury (2.67 kilopascals) five minutes after exercise. Changes in relative oxygenation were measured with use of the non-invasive method of near-infrared spectroscopy. In all patients and subjects, there was rapid relative deoxygenation after the initiation of exercise, the level of oxygenation remained relatively stable during continued exercise, and there was reoxygenation to a level that exceeded the pre-exercise resting level after the cessation of exercise. During exercise, maximum relative deoxygenation in the patients who had chronic compartment syndrome (mean relative deoxygenation [and standard error], -290 +/- 39 millivolts) was significantly greater than that in the patients who did not have chronic compartment syndrome (-190 +/- 10 millivolts) and that in the control subjects (-179 +/- 14 millivolts) (p < 0.05 for both comparisons). In addition, the interval between the cessation of exercise and the recovery of the pre-exercise resting level of oxygenation was significantly longer for the patients who had chronic compartment syndrome (184 +/- 54 seconds) than for the patients who did not have chronic compartment syndrome (39 +/- 19 seconds) and the control subjects (33 +/- 10 seconds) (p < 0.05 for both comparisons).

NASA Discipline Musculoskeletal↗
NASA NTRS1997

Near-infrared spectroscopy for monitoring of tissue oxygenation of exercising skeletal muscle in a chronic compartment syndrome model

Variations in the levels of muscle hemoglobin and of myoglobin oxygen saturation can be detected non-invasively with near-infrared spectroscopy. This technique could be applied to the diagnosis of chronic compartment syndrome, in which invasive testing has shown increased intramuscular pressure associated with ischemia and pain during exercise. We simulated chronic compartment syndrome in ten healthy subjects (seven men and three women) by applying external compression, through a wide inflatable cuff, to increase the intramuscular pressure in the anterior compartment of the leg. The tissue oxygenation of the tibialis anterior muscle was measured with near-infrared spectroscopy during gradual inflation of the cuff to a pressure of forty millimeters of mercury (5.33 kilopascals) during fourteen minutes of cyclic isokinetic dorsiflexion and plantar flexion of the ankle. The subjects exercised with and without external compression. The data on tissue oxygenation for each subject then were normalized to a scale of 100 per cent (the baseline value, or the value at rest) to 0 per cent (the physiological minimum, or the level of oxygenation achieved by exercise to exhaustion during arterial occlusion of the lower extremity). With external compression, tissue oxygenation declined at a rate of 1.4 +/- 0.3 per cent per minute (mean and standard error) during exercise. After an initial decrease at the onset, tissue oxygenation did not decline during exercise without compression. The recovery of tissue oxygenation after exercise was twice as slow with compression (2.5 +/- 0.6 minutes) than it was without the use of compression (1.3 +/- 0.2 minutes).

NASA Discipline Musculoskeletal↗
NASA NTRS1995

Oral branched-chain amino acids decrease whole-body proteolysis

BACKGROUND: This study reports the effects of ingesting branched-chain amino acids (leucine, valine, and isoleucine) on protein metabolism in four men. METHODS: To calculate leg protein synthesis and breakdown, we used a new model that utilized the infusion of L-[ring-13C6]phenylalanine and the sampling of the leg arterial-venous difference and muscle biopsies. In addition, protein-bound enrichments provided for the direct calculation of muscle fractional synthetic rate. Four control subjects ingested an equivalent amount of essential amino acids (threonine, methionine, and histidine) to discern the effects of branched-chain amino acid nitrogen vs the effects of essential amino acid nitrogen. Each drink also included 50 g of carbohydrate. RESULTS: Consumption of the branched-chain and the essential amino acid solutions produced significant threefold and fourfold elevations in their respective arterial concentrations. Protein synthesis and breakdown were unaffected by branched-chain amino acids, but they increased by 43% (p < .05) and 36% (p < .03), respectively, in the group consuming the essential amino acids. However, net leg balance of phenylalanine was unchanged by either drink. Direct measurement of protein synthesis by tracer incorporation into muscle protein (fractional synthetic rate) revealed no changes within or between drinks. Whole-body phenylalanine flux was significantly suppressed by each solution but to a greater extent by the branched-chain amino acids (15% and 20%, respectively) (p < .001). CONCLUSIONS: These results suggest that branched-chain amino acid ingestion suppresses whole-body proteolysis in tissues other than skeletal muscle in normal men.

NASA Discipline Number 18-10↗
NASA NTRS2000

The neuropathic postural tachycardia syndrome

BACKGROUND: The postural tachycardia syndrome is a common disorder that is characterized by chronic orthostatic symptoms and a dramatic increase in heart rate on standing, but that does not involve orthostatic hypotension. Several lines of evidence indicate that this disorder may result from sympathetic denervation of the legs. METHODS: We measured norepinephrine spillover (the rate of entry of norepinephrine into the venous circulation) in the arms and legs both before and in response to exposure to three stimuli (the cold pressor test, sodium nitroprusside infusion, and tyramine infusion) in 10 patients with the postural tachycardia syndrome and in 8 age- and sex-matched normal subjects. RESULTS: At base line, the mean (+/-SD) plasma norepinephrine concentration in the femoral vein was lower in the patients with the postural tachycardia syndrome than in the normal subjects (135+/-30 vs. 215+/-55 pg per milliliter [0.80+/-0.18 vs. 1.27+/-0.32 nmol per liter], P=0.001). Norepinephrine spillover in the arms increased to a similar extent in the two groups in response to each of the three stimuli, but the increases in the legs were smaller in the patients with the postural tachycardia syndrome than in the normal subjects (0.001+/-0.09 vs. 0.12+/-0.12 ng per minute per deciliter of tissue [0.006+/-0.53 vs. 0.71+/-0.71 nmol per minute per deciliter] with the cold pressor test, P=0.02; 0.02+/-0.07 vs. 0.23+/-0.17 ng per minute per deciliter [0.12+/-0.41 vs. 1.36+/-1.00 nmol per minute per deciliter] with nitroprusside infusion, P=0.01; and 0.008+/-0.09 vs. 0.19+/-0.25 ng per minute per deciliter [0.05+/-0.53 vs. 1.12+/-1.47 nmol per minute per deciliter] with tyramine infusion, P=0.04). CONCLUSIONS: The neuropathic postural tachycardia syndrome results from partial sympathetic denervation, especially in the legs.

NASA Discipline Regulatory Physiology↗