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At least 37 records · Page 2

Low LBNP Tolerance in Men is Associated With Attenuated Activation of The Renin-Angiotensin System

Vasoactive hormone concentrations [epinephrine (pE), norepinephrine (pNE), angiotensin II (pATII), vasopressin (pVP), endothelin 1 (pET1)] and plasma renin activity (pRA) were measured during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system is related to LBNP tolerance. Healthy men (2,822 cal/day(exp -1), 2 mmol*kg(exp -1)*day(exp -1)) Na(+)) were exposed to 30 minutes of progressive LBNP to -50 mmHg. LBNP was uneventful for seven men (25 +/- 2 years, HiTol group), but eight men (26 +/- 3 years) reached pre-syncope after 11 +/- 1 minutes (P < 0.001, LoTol group). Mean arterial pressure was unchanged. Central venous pressure and left atrial diameter decreased in both groups (5-6 mmHg by approx. 30%, P < 0.05). Control [hormone] were similar but, pRA differed between groups (LoTol 0.6 +/- 0.1, HiTol 1.2 +/- 0.1 ng Ang1/(ml(exp -1)*h(exp -1)), P < 0.05). LBNP increased (P < 0.05) pRA and pATII more in HiTol (9.9 +/- 2.2 ng Ang1/(ml(exp -1)*h(exp -1)) and 58 +/- 12 pg/ml(exp -1)) than LoTol (4.3 +/- 0.9 ng Ang1/(ml*h) and 28 +/- 6 pg/ml(exp -1)). In contrast, pVP was higher (P < 0.05) in LoTol than in HiTol. The response of the renin-angiotensin system seems linked to the occurrence of pre-syncope, and measurement of resting pRA may be predictive.

Greenleaf, J. E.↗

Bursting into space: alterations of sympathetic control by space travel

AIM: Astronauts return to Earth with reduced red cell masses and hypovolaemia. Not surprisingly, when they stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied autonomic function in six male astronauts (average +/- SEM age: 40 +/- 2 years) before, during, and after the 16-day Neurolab space shuttle mission. METHOD: We recorded electrocardiograms, finger photoplethysmographic arterial pressures, respiration, peroneal nerve muscle sympathetic activity, plasma noradrenaline and noradrenaline kinetics, and cardiac output, and we calculated stroke volume and total peripheral resistance. We perturbed autonomic function before and during spaceflight with graded Valsalva manoeuvres and lower body suction, and before and after the mission with passive upright tilt. RESULTS: In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33%) in three subjects, in whom noradrenaline spillover and clearance also were increased. Valsalva straining provoked greater reductions of arterial pressure, and proportionally greater sympathetic responses in space than on Earth. Lower body suction elicited greater increases of sympathetic nerve activity, plasma noradrenaline, and noradrenaline spillover in space than on Earth. After the Neurolab mission, left ventricular stroke volume was lower and heart rate was higher during tilt, than before spaceflight. No astronaut experienced orthostatic hypotension or pre-syncope during 10 min of post-flight tilting. CONCLUSION: We conclude that baseline sympathetic outflow, however measured, is higher in space than on earth, and that augmented sympathetic nerve responses to Valsalva straining, lower body suction, and post-flight upright tilt represent normal adjustments to greater haemodynamic stresses associated with hypovolaemia.

NASA Program Biomedical Research and Countermeasur↗

Resistance exercise training and the orthostatic response

Resistance exercise has been suggested to increase blood volume, increase the sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and decrease leg compliance, all factors that are expected to improve orthostatic tolerance. To further test these hypotheses, cardiovascular responses to standing and to pre-syncopal limited lower body negative pressure (LBNP) were measured in two groups of sedentary men before and after a 12-week period of either exercise (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted of nine isotonic exercises, four sets of each, 3 days per week, stressing all major muscle groups. After exercise training, leg muscle volumes increased (P < 0.05) by 4-14%, lean body mass increased (P = 0.00) by 2.0 (0.5) kg, leg compliance and BARO were not significantly altered, and the maximal LBNP tolerated without pre-syncope was not significantly different. Supine resting heart rate was reduced (P = 0.03) without attenuating the heart rate or blood pressure responses during the stand test or LBNP. Also, blood volume (125I and 51Cr) and red cell mass were increased (P < 0.02) by 2.8% and 3.9%, respectively. These findings indicate that intense resistance exercise increases blood volume but does not consistently improve orthostatic tolerance.

NASA Discipline Musculoskeletal↗

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

NASA Discipline Number 14-10↗

Orthostasis: exercise and exercise training

There are two major problems here that are not independent. One is the more practically oriented problem of determining the effect of various modes of exercise training on gravitational tolerances, i.e., the point of syncope (unconsciousness) usually estimated from the time of appearance of presyncopal signs and symptoms. The other is more theoretical and concerns the mechanism of blood pressure failure that results in syncope. In many experimental designs these two problems or purposes have been intermingled, with equivocal results.

Review, Tutorial↗

Gender Differences in Cardiovascular Tolerance to Short Arm Centrifugation

In preparation for the NASA Artificial Gravity (AG) pilot study, the tolerability of the proposed AG parameters was tested in 11 ambulatory human subjects (6m, 5w) by exposing each to a short arm centrifuge trial. Subjects were oriented in the supine position (but inclined 6deg head down) on one arm of the centrifuge, and the rotation rate (30.6-33.4 rpm) and radial position of the feet were set to produce 2.5G of equivalent gravitational load at the force plate directly beneath the feet, 1G at the level of the mediastinum, and approximately 0.55G at the labyrinth. Amongst the 6 men participating in this preliminary study, 5 completed at least 60 minutes of the trial successfully with no adverse sequelae. However, amongst the female cohort the test was stopped by the medical monitor before 60 min in all but one case, with pre-syncope listed as the reason for termination in all cases. Mean time before abort of the centrifuge run amongst the women was 33.2 +/- 20.97 min. It is known that women have a greater predisposition to syncope during orthostatic stress, under normal tilt table conditions, during LBNP, and following space flight. The reasons for this difference are the subject of some debate, but anthropometric factors, the vasoactive effects of sex hormones, gender differences in susceptibility to motion sickness, catecholamine levels, ability to augment total peripheral resistance in response to orthostatic stress, and structural differences in cardiac anatomy and physiology have all been suggested. This finding led to the exclusion of women from the AG pilot study. Clearly if AG is to be employed as a multi-system countermeasure it must provide physiological protection at rotation rates within the tolerance limits of all potential astronauts. Further investigation of the responses of women to centrifugation will be necessary to determine how to adjust AG parameters for tolerance by female subjects before a more detailed investigation of the appropriate dose in terms of G load, rotation rate, exposure duration and frequency can be performed.

Fong, Kevin J.↗

Association between vasovagal hypotension and low sympathetic neural activity during presyncope

Recent studies suggest that an underlying mechanism for susceptibility of patients and astronauts to presyncope includes hypoadrenergic responses to orthostatic stress. However, data used to reach this conclusion are open to various interpretations. In this report, maintenance of sympathetic neural activity (MSNA; peroneal nerve microneurography) during -60 mmHg lower body negative pressure (LBNP) was associated with maintenance of orthostatic tolerance, and disappearance of MSNA was associated with hypotension and pre-syncope. However, MSNA was substantially higher during progressive increases of negative pressure in the presyncopal subject, compared to the non-presyncopal subjects. The data from this case report question the notion that orthostatic hypotension occurs due to inadequate sympathetic neural activation during orthostatic stress in apparently normal, healthy subjects.

Case Reports↗

Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects

Cardiovascular responses during a graded lower body negative pressure (LBNP) protocol were compared before and after atropine and propranolol administration to test the hypothesis that both sympathetic and parasympathetic control of cardio-acceleration are associated with syncopal predisposition to orthostatic stress in healthy subjects. Eleven men were categorized into two groups having high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before the onset of presyncopal symptoms. HT and LT groups were similar in physical characteristics, fitness, and baseline cardiovascular measurements. Atropine treatment had no effect on LBNP tolerance or mean arterial pressure at presyncope, despite an atropine-induced increase in heart rate. Propranolol treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP tolerance after propranolol administration was associated with reductions in cardiac output, whereas increase in systemic peripheral resistance from baseline to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP tolerance after beta blockade reflected a chronotropic effect because lower LBNP tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without significant effects on stroke volume at presyncope. Absence of an atropine-induced difference in cardiac output and systemic peripheral resistance between HT and LT groups failed to support the notion that cardiac vagal withdrawal represents a predominant mechanism that could account for differences in orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT groups after propranolol treatment was most closely associated with reduced tachycardia, the data suggest that a primary autonomically mediated mechanism for maintenance of mean arterial pressure and orthostatic tolerance in healthy subjects is beta adrenergic-induced tachycardia.

Non-NASA Center↗

Lower body negative pressure, experiment M092

Evaluation of orthostatic intolerance has been achieved by the use of lower body negative pressure (LBNP). The LBNP technique, though independent of gravity, simulates its effect by exposing the legs and the lower abdomen to reduced ambient pressures. This LBNP experiment, conducted during the 56-day simulation of the Skylab environment, was designed to supply baseline information on cardiovascular responses to periodic orthostatic stress. Impaired orthostatic tolerance, manifested by the increased heart rate, diminished systolic and pulse pressure, and increased tendency to syncope in the upright position, or during LBNP, was not observed in this experiment.

Johnson, R. L.↗

Skylab experiment M-092 - Results of the first manned mission

Blood pressure, heart rate, and percentage increase in leg volume were continuously recorded for the Inflight Lower Body Negative Pressure (LBNP) experiment conducted during the first manned Skylab mission. Data were collected over a 5-month preflight period as well as at approximately 3-day intervals throughout the mission. Individual variations in cardiovascular responses to LBNP during the preflight period continued to be demonstrated inflight, and measurements of the calf showed that a large volume of fluid was shifted out of the legs early in the flight. A much greater increase in leg volume occurred during inflight LBNP than in preflight tests. Resting heart rates tended to be low early in the flight and to increase slightly as it progressed, while resting blood pressure varied. The LBNP protocol was a greater stress inflight, and the tests had to be stopped early on three occasions due to impending syncopal reactions. Inflight LBNP responses seemed to predict the degree of postflight orthostatic intolerance. Postflight responses to LBNP during the first 48 hours were characterized by marked elevations in heart rate, instability in blood pressure, and considerably elevated systolic and diastolic pressures both at rest and during stress.

Johnson, R. L.↗

Specialized physiological studies in support of manned space flight

Subjects were tested for tolerance to lower body negative pressure (LBNP) before and after acute dehydration by working intermittenly for two hours without fluid replacement. On the second day there-after the LBNP tests were repeated before and after acute dehydration. The LBNP test consisted of 5 min long consective stages at -20, -30, -40, -50 and -60 Torr. Tests were terminated when syncope was imminent or the full sequence was completed. Tolerance was expressed in terms of cumulative stress in Torr x min. Measurements of body mass, density, fat fraction and total body water (TBW) were made before and after acclimation. Blood volume and its constituents were determined before and after each of the four LBNP tests. During LBNP, heart rate, blood pressure, and changes in calf and forearm volume were recorded every minute. Results showed: acute dehydration caused a significant loss in average LBNP tolerance on all subjects. Acclimation to heat did not significantly affect LBNP tolerance in hydrated subjects but significantly improved it on dehydrated subjects.

Luft, U. C.↗

Cardiovascular responses of men and women to lower body negative pressure

Changes in blood flow and blood redistribution were measured by impedance plethysmography in the pelvic and leg regions of six male and four female subjects during three 5-min exposures to -20, -40, and -60 mm Hg lower body negative pressure (LBNP). Female subjects demonstrated significantly higher mean heart rate and lower leg blood flow indices than the male subjects during the recumbent control periods. Men had slightly higher mean resting systolic and diastolic blood pressures and higher mean control pelvic blood indices. Women demonstrated significantly less blood pooling in the legs and slightly less in the pelvic region than the men. All of the 18 tests with male subjects at -60 mm Hg were completed without initial signs of syncope, while only two of the tests with women were completed successfully without the subject exhibiting presyncopal conditions. Results indicate that impedance plethysmography can be used to measure segmental cardiovascular responses during LBNP and that females may be less tolerant to -60 mm Hg LBNP than males.

Montgomery, L. D.↗

Pioneering in gravitational physiology

Gravity affects biology at almost all levels above that of the cell organelle. Attention is presently given to progress made in the understanding of gravitational effects through studies employing centrifuges, clinostats, inverted preparations, linear devices, water immersion, free fall, and short- and long-term spaceflight. The cardiovascular changes which cause malaise and illness during the first few days of extended space missions are the direct result of fluid translocation from the lower extremities. Upon reentry, there is hypovolumnia and a cardiovascular deconditioning that can include tachycardia, changes in arterial blood pressure, narrow pulse pressure, and syncope. Attention is also given to NASA's gravitational physiology reseach program.

Soffen, G. A.↗

Exercise training - Blood pressure responses in subjects adapted to microgravity

Conventional endurance exercise training that involves daily workouts of 1-2 hr duration during exposure to microgravity has not proven completely effective in ameliorating postexposure orthostatic hypotension. Single bouts of intense exercise have been shown to increase plasma volume and baroreflex sensitivity in ambulatory subjects through 24 hr postexercise and to reverse decrements in maximal oxygen uptake and syncopal episodes following exposure to simulated microgravity. These physiological adaptations to acute intense exercise were opposite to those observed following exposure to microgravity. These results suggest that the 'exercise training' stimulus used to prevent orthostatic hypotension induced by microgravity may be specific and should be redefined to include single bouts of maximal exercise which may provide an acute effective countermeasure against postflight hypotension.

Convertino, Victor A.↗

Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt

This study investigates cerebral blood flow (CBF) velocity in humans before, during, and after 24 h of 6 deg head-down tilt (HDT), which is a currently accepted experimental model to simulate microgravity. CBF velocity was measured by use of the transcranial Doppler technique in the right middle cerebral artery of eight healthy male subjects. Mean CBF velocity increased from the pre-HDT upright seated baseline value of 55.5 +/- 3.7 (SE) cm/s to 61.5 +/- 3.3 cm/s at 0.5 h of HDT, reached a peak value of 63.2 +/- 4.1 cm/s at 3 h of HDT, and remained significantly above the pre-HDT baseline for over 6 h of HDT. During upright seated recovery, mean CBF velocity decreased to 87 percent of the pre-HDT baseline value. Mean CBF velocity correlated well with calculated intracranial arterial pressure (IAP). As analyzed by linear regression, mean CBF velocity = 29.6 + 0.32IAP. These results suggest that HDT increases CBF velocity by increasing IAP during several hours after the onset of microgravity. Importantly, the decrease in CBF velocity after HDT may be responsible, in part, for the increased risk of syncope observed in subjects after prolonged bed rest and also in astronauts returning to Earth.

Kawai, Y.↗

Responses to LBNP in men with varying profiles of strength and aerobic capacity: Implications for flight crews

Hemodynamic and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic stress is associated with strength and/or aerobic capacity. Subjects underwent treadmill tests to determine peak oxygen uptake (peak VO2) and isokinetic dynamo meter tests to determine leg strength. Based on predetermined criteria, the subjects were classified into one of four fitness profiles of six subjects each matched for age, height, and weight: (1) low strength/low aerobic fitness; (2) low strength/high aerobic fitness; (3) high strength/low aerobic fitness; and (4) high strength/high aerobic fitness. Following 90 min of 6 degree head-down tilt (HDT), each subject underwent graded LBNP through -50 mmHg or presyncope, with maximal duration 15 min. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences except for catecholamines. Seven subjects, distributed among the four fitness profiles, became presyncopal. Subjects who showed greatest reduction in mean arterial pressure (MAP) during LBNP had greater elevations in vasopressin and lesser increases in heart rate and peripheral resistance. Peak VO2 nor leg strength were correlated with fall in MAP or with syncopal episodes. We conclude that neither aerobic nor strength fitness characteristics are good predictors of responses to LBNP stress.

Convertino, Victor A.↗

The Effects of Liquid Cooling Garments on Post-Space Flight Orthostatic Intolerance

Post space flight orthostatic intolerance among Space Shuttle crew members following exposure to extended periods of microgravity has been of significant concern to the safety of the shuttle program. Following the Challenger accident, flight crews were required to wear launch and entry suits (LES). It was noted that overall, there appeared to be a higher degree of orthostatic intolerance among the post-Challenger crews (approaching 30%). It was hypothesized that the increased heat load incurred when wearing the LES, contributed to an increased degree of orthostatic intolerance, possibly mediated through increased peripheral vasodilatation triggered by the heat load. The use of liquid cooling garments (LCG) beneath the launch and entry suits was gradually implemented among flight crews in an attempt to decrease heat load, increase crew comfort, and hopefully improve orthostatic tolerance during reentry and landing. The hypothesis that the use of the LCG during reentry and landing would decrease the degree of orthostasis has not been previously tested. Operational stand-tests were performed pre and post flight to assess crewmember's cardiovascular system's ability to respond to gravitational stress. Stand test and debrief information were collected and databased for 27 space shuttle missions. 63 crewpersons wearing the LCG, and 70 crewpersons not wearing the LCG were entered into the database for analysis. Of 17 crewmembers who exhibited pre-syncopal symptoms at the R+O analysis, 15 were not wearing the LCG. This corresponds to a 21% rate of postflight orthostatic intolerance among those without the LCG, and a 3% rate for those wearing LCG. There were differences in these individual's average post-flight maximal systolic blood pressure, and lower minimal Systolic Blood pressures in those without LCG. Though other factors, such as type of fluid loading, and exercise have improved concurrently with LCG introduction, from this data analysis, it appears that LCG usage provided a significant degree of protection from post-flight orthostatic intolerance.

Billica, Roger↗

Aerobic Fitness Does Not Contribute to Prediction of Orthostatic Intolerance

Several investigations have suggested that orthostatic tolerance may be inversely related to aerobic fitness (VO (sub 2max)). To test this hypothesis, 18 males (age 29 to 51 yr) underwent both treadmill VO(sub 2max) determination and graded lower body negative pressures (LBNP) exposure to tolerance. VO(2max) 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 initial accumulation were measured at rest and during the final minute of LBNP. For all 18 subjects, mean (plus or minus SE) fluid accumulation index and leg venous compliance index at peak LBNP were 139 plus or minus 3.9 plus or minus 0.4 ml-torr-min(exp -2) x 10(exp 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 VO(sub 2max) and percent body fat were not found to correlate significantly (P is 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.

Convertino, Victor A.↗