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Biomedical subjects

Benjamin D Levine

Publications and source records attributed to Benjamin D Levine.

At least 55 records · Page 3Linked to original sources

Effect of aging and physical activity on left ventricular compliance.

BACKGROUND: Left ventricular compliance appears to decrease with aging, which may contribute to the high incidence of heart failure in the elderly. However, whether this change is an inevitable consequence of senescence or rather secondary to reduced physical activity is unknown. METHODS AND RESULTS: Twelve healthy sedentary seniors (69.8+/-3 years old; 6 women, 6 men) and 12 Masters athletes (67.8+/-3 years old; 6 women, 6 men) underwent pulmonary artery catheterization to define Starling and left ventricular pressure-volume curves. Data were compared with those obtained in 14 young but sedentary control subjects (28.9+/-5 years old; 7 women, 7 men). Pulmonary capillary wedge pressures and left ventricular end-diastolic volumes by use of echocardiography were measured at baseline, during decreased cardiac filling by use of lower-body negative pressure (-15 and -30 mm Hg), and after saline infusion (15 and 30 mL/kg). Stroke volume for any given filling pressure was greater in Masters athletes compared with the age-matched sedentary subjects, whereas contractility, as assessed by preload recruitable stroke work, was similar. There was substantially decreased left ventricular compliance in healthy but sedentary seniors compared with the young control subjects, which resulted in higher cardiac pressures for a given filling volume and higher myocardial wall stress for a given strain. The pressure-volume curve for the Masters athletes was indistinguishable from that of the young, sedentary control subjects. CONCLUSIONS: A sedentary lifestyle during healthy aging is associated with decreased left ventricular compliance, leading to diminished diastolic performance. Prolonged, sustained endurance training preserves ventricular compliance with aging and may help to prevent heart failure in the elderly.

Aged↗

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.

Adult↗

Cerebral hemodynamics during the Valsalva maneuver: insights from ganglionic blockade.

BACKGROUND AND PURPOSE: The aim of this study was to differentiate the mechanical effects of the Valsalva maneuver (VM) from the effects of changes in autonomic neural activity on cerebral hemodynamics in humans. METHODS: Nine healthy subjects performed the VM before and after autonomic ganglionic blockade with trimethaphan. Blood pressure (BP) was measured in the radial artery with an indwelling catheter or at the finger by Finapres. Cerebral blood flow (CBF) velocity was measured in the middle cerebral artery with transcranial Doppler; end-tidal CO2 was measured by mass spectrometry. RESULTS: Before blockade, during phase II of the VM, BP was reduced by 27% and CBF velocity was reduced by 33% (magnitude of changes during phase II divided by baseline measurements before the VM, P<0.05). Cerebrovascular conductance index (CVCI) increased by 21%. During phase IV, overshoot of CBF velocity was proportionately greater than that of BP (46% versus 30%). After blockade, during phase II, BP fell to a much greater degree by 50%, while CBF velocity decreased even more by 60% associated with an increase in CVCI by 33%. During phase IV, despite the absence of BP overshoot, CBF velocity still increased by 55% and CVCI by 33%. Both were significantly greater than before blockade. CONCLUSIONS: After ganglionic blockade, cerebral autoregulation is unable to prevent the substantial fall in CBF induced by the marked reduction in BP during the VM. Enhanced phase IV increases in both CBF velocity and CVCI reflect the intrinsic characteristics of cerebral hyperemic responses, which are likely modified in part by the removal of vasoconstrictor effects of autonomic neural activity elicited during the VM.

Adult↗

Inhibition of nitric oxide synthase does not alter dynamic cerebral autoregulation in humans.

The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). NOS was inhibited by intravenous NG-monomethyl-L-arginine (L-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. Pressor effects of L-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, L-NMMA increased mean BP from 83+/-3 to 94+/-3 mmHg (P < 0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% (P < 0.05). BP and CBF velocity variability and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with L-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that increase in CVRI after L-NMMA was mediated myogenically by increase in arterial pressure rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without L-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at low frequencies increased in parallel by 277% and 217%, respectively (P < 0.05). However, transfer function gain remained unchanged. During tilt with L-NMMA, changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without L-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans.

Adult↗

Intermittent normobaric hypoxia does not alter performance or erythropoietic markers in highly trained distance runners.

This study was designed to test the hypothesis that intermittent normobaric hypoxia at rest is a sufficient stimulus to elicit changes in physiological measures associated with improved performance in highly trained distance runners. Fourteen national-class distance runners completed a 4-wk regimen (5:5-min hypoxia-to-normoxia ratio for 70 min, 5 times/wk) of intermittent normobaric hypoxia (Hyp) or placebo control (Norm) at rest. The experimental group was exposed to a graded decline in fraction of inspired O2: 0.12 (week 1), 0.11 (week 2), and 0.10 (weeks 3 and 4). The placebo control group was exposed to the same temporal regimen but breathed fraction of inspired O2 of 0.209 for the entire 4 wk. Subjects were matched for training history, gender, and baseline measures of maximal O2 uptake and 3,000-m time-trial performance in a randomized, balanced, double-blind design. These parameters, along with submaximal treadmill performance (economy, heart rate, lactate, and ventilation), were measured in duplicate before, as well as 1 and 3 wk after, the intervention. Hematologic indexes, including serum concentrations of erythropoietin and soluble transferrin receptor and reticulocyte parameters (flow cytometry), were measured twice before the intervention, on days 1, 5, 10, and 19 of the intervention, and 10 and 25 days after the intervention. There were no significant differences in maximal O2 uptake, 3,000-m time-trial performance, erythropoietin, soluble transferrin receptor, or reticulocyte parameters between groups at any time. Four weeks of a 5:5-min normobaric hypoxia exposure at rest for 70 min, 5 days/wk, is not a sufficient stimulus to elicit improved performance or change the normal level of erythropoiesis in highly trained runners.

Adult↗

Hemodynamics of orthostatic intolerance: implications for gender differences.

Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 +/- 55.0 vs. 927.7 +/- 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 +/- 2.0 vs. 7.1 +/- 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 +/- 0.8 vs. 4.29 +/- 0.6 ml.m-2.mmHg-1, P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance.

Adult↗

Comparison of coronary artery calcium detected by electron beam tomography in patients with to those without symptomatic coronary heart disease.

Although the presence of coronary artery calcium (CAC) has been associated with the prevalence and incidence of coronary heart disease (CHD), it is unclear if this association has a threshold or a continuous relation. The aim of this research was to explore the relation between CAC, as detected by electron beam tomography (EBT), and CHD in a cross-sectional study of women and men who presented to a single center for elective screening with EBT from 1995 to 1998. Of 17,967 participants, patients with CHD had higher CAC levels than those without CHD. Using subjects without CAC as the referent group, the odds ratios for prevalent CHD increased significantly across increasing quartiles of CAC in the overall population and in both genders. In a subset of the population, after adjusting for CHD risk factors, CAC scores in the fourth quartile were associated with an odds ratio of 33.8 (p <0.001) for prevalent CHD. Among patients with and without CHD, men were more likely than women to have detectable CAC (58.1% vs 28.3% and 96.1% vs 68.9% respectively, p <0.001 for each); the prevalence of detectable CAC increased with age and was higher in men than in women. There was an increased risk for prevalent CHD at all levels of CAC >0, with the greatest increase in risk occurring in patients with CAC scores >95. These observations support the potential of EBT as a sensitive test for detection of CHD.

Adult↗

Obesity: associations with acute mountain sickness.

BACKGROUND: Although few retrospective studies of high altitude have reported that obesity might be associated with the development of acute mountain sickness (AMS), this association has not been studied prospectively. OBJECTIVE: To determine whether obesity is associated with the development of AMS. DESIGN: Obese and nonobese men were compared at a simulated altitude of 3658 m (12 000 ft). SETTING: 24 hours in a hypobaric environmental chamber. PARTICIPANTS: 9 obese and 10 nonobese men. MEASUREMENTS: Percentage body fat (by hydrostatic weighing), Lake Louise AMS score, and Sao2 level (by pulse oximetry) were measured. RESULTS: Average AMS scores increased more rapidly with time spent at simulated high altitudes for obese men than for nonobese men (P < 0.001). The response of Sao2 with exposure differed between nonobese and obese men. After 24 hours in the altitude chamber, seven obese men (78%) and four nonobese men (40%) had AMS scores of 4 or more. CONCLUSION: Obesity seems to be associated with the development of AMS, which may be partly related to greater nocturnal desaturation with altitude exposure.

Adult↗

Exercise throughout 6 degrees head-down tilt bed rest preserves thermoregulatory responses.

Spaceflight and its bed rest analog [6 degrees head-down tilt (HDT)] decrease plasma and blood volume and aerobic capacity. These responses may be associated with impaired thermoregulatory responses observed during exercise and passive heating after HDT exposure. This project tested the hypothesis that dynamic exercise during 13 days of HDT bed rest preserves thermoregulatory responses. Throughout HDT bed rest, 10 subjects exercised for 90 min/day (75% of pre-HDT maximum heart rate; supine). Before and after HDT bed rest, each subject exercised in the supine position at the same workload in a 28 degrees C room. The internal temperature (Tcore) threshold for the onset of sweating and cutaneous vasodilation, as well as the slope of the relationship between the elevation in Tcore relative to the elevation in sweat rate (SR) and cutaneous vascular conductance (CVC; normalized to local heating maximum), were quantified pre- and post-HDT. Tcore thresholds for the onset of cutaneous vasodilation on the chest and forearm (chest: 36.79 +/- 0.12 to 36.94 +/- 0.13 degrees C, P = 0.28; forearm: 36.76 +/- 0.12 to 36.91 +/- 0.11 degrees C, P = 0.16) and slope of the elevation in CVC relative to Tcore (chest: 77.9 +/- 14.2 to 80.6 +/- 17.2%max/ degrees C; P = 0.75; forearm: 76.3 +/- 11.8 to 67.5 +/- 14.3%max/ degrees C, P = 0.39) were preserved post-HDT. Moreover, the Tcore threshold for the onset of SR (36.66 +/- 0.12 to 36.74 +/- 0.10 degrees C; P = 0.36) and the slope of the relationship between the elevation in SR and the elevation in Tcore (1.23 +/- 0.19 to 1.01 +/- 0.14 mg x cm(-2) x min(-1) x degrees C(-1); P = 0.16) were also maintained. Finally, after HDT bed rest, peak oxygen uptake and plasma and blood volumes were not different relative to pre-HDT bed rest values. These data suggest that dynamic exercise during this short period of HDT bed rest preserves thermoregulatory responses.

Adult↗

Nitric oxide synthase inhibition does not affect regulation of muscle sympathetic nerve activity during head-up tilt.

To test the hypothesis that systemic inhibition of nitric oxide (NO) synthase does not alter the regulation of sympathetic outflow during head-up tilt in humans, in eight healthy subjects NO synthase was blocked by intravenous infusion of NG-monomethyl-L-arginine (L-NMMA). Blood pressure, heart rate, cardiac output, total peripheral resistance (TPR), and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and during 60 degrees head-up tilt. In the supine position, infusion of L-NMMA increased blood pressure, via increased TPR, and inhibited MSNA. However, the increase in MSNA evoked by head-up tilt during L-NMMA infusion (change in burst rate: 24 +/- 4 bursts/min; change in total activity: 209 +/- 36 U/min) was similar to that during head-up tilt without L-NMMA (change in burst rate: 23 +/- 4 bursts/min; change in total activity: 251 +/- 52 U/min, n = 6, all P > 0.05). Moreover, changes in TPR and heart rate during head-up tilt were virtually identical between the two conditions. These results suggest that systemic inhibition of NO synthase with L-NMMA does not affect the regulation of sympathetic outflow and vascular resistance during head-up tilt in humans.

Adult↗

Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?

Occupational or recreational exercise reduces mortality from cardiovascular disease. The potential mechanisms for this reduction may include changes in blood pressure (BP) and autonomic control of the circulation. Therefore, we conducted the present long-term longitudinal study to quantify the dose-response relationship between the volume and intensity of exercise training, and regulation of heart rate (HR) and BP. We measured steady-state hemodynamics and analyzed dynamic cardiovascular regulation by spectral and transfer function analysis of cardiovascular variability in 11 initially sedentary subjects during 1 yr of progressive endurance training sufficient to allow them to complete a marathon. From this, we found that 1) moderate exercise training for 3 mo decreased BP, HR, and total peripheral resistance, and increased cardiovascular variability and arterial baroreflex sensitivity; 2) more prolonged and intense training did not augment these changes further; and 3) most of these changes returned to control values at 12 mo despite markedly increased training duration and intensity equivalent to that routinely observed in competitive athletes. In conclusion, increases in R-wave-R-wave interval and cardiovascular variability indexes are consistent with an augmentation of vagal modulation of HR after exercise training. It appears that moderate doses of training for 3 mo are sufficient to achieve this response as well as a modest hypotensive effect from decreasing vascular resistance. However, more prolonged and intense training does not necessarily lead to greater enhancement of circulatory control and, therefore, may not provide an added protective benefit via autonomic mechanisms against death by cardiovascular disease.

Adaptation, Physiological↗

Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans.

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.

Adult↗

Cardiovascular and sympathetic neural responses to handgrip and cold pressor stimuli in humans before, during and after spaceflight.

Astronauts returning to Earth have reduced orthostatic tolerance and exercise capacity. Alterations in autonomic nervous system and neuromuscular function after spaceflight might contribute to this problem. In this study, we tested the hypothesis that exposure to microgravity impairs autonomic neural control of sympathetic outflow in response to peripheral afferent stimulation produced by handgrip and a cold pressor test in humans. We studied five astronauts approximately 72 and 23 days before, and on landing day after the 16 day Neurolab (STS-90) space shuttle mission, and four of the astronauts during flight (day 12 or 13). Heart rate, arterial pressure and peroneal muscle sympathetic nerve activity (MSNA) were recorded before and during static handgrip sustained to fatigue at 40 % of maximum voluntary contraction, followed by 2 min of circulatory arrest pre-, in- and post-flight. The cold pressor test was applied only before (five astronauts) and during flight (day 12 or 13, four astronauts). Mean (+/- S.E.M.) baseline heart rates and arterial pressures were similar among pre-, in- and post-flight measurements. At the same relative fatiguing force, the peak systolic pressure and mean arterial pressure during static handgrip were not different before, during and after spaceflight. The peak diastolic pressure tended to be higher post- than pre-flight (112 +/- 6 vs. 99 +/- 5 mmHg, P = 0.088). Contraction-induced rises in heart rate were similar pre-, in- and post-flight. MSNA was higher post-flight in all subjects before static handgrip (26 +/- 4 post- vs. 15 +/- 4 bursts min(-1) pre-flight, P = 0.017). Contraction-evoked peak MSNA responses were not different before, during, and after spaceflight (41 +/- 4, 38 +/- 5 and 46 +/- 6 bursts min(-1), all P > 0.05). MSNA during post-handgrip circulatory arrest was higher post- than pre- or in-flight (41 +/- 1 vs. 33 +/- 3 and 30 +/- 5 bursts min(-1), P = 0.038 and 0.036). Similarly, responses of MSNA and blood pressure to the cold pressor test were well maintained in-flight. We conclude that modulation of muscle sympathetic neural outflow by muscle metaboreceptors and skin nociceptors is preserved during short duration spaceflight.

Adult↗

Cyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11.

Combining anticancer drugs with different mechanisms of action has the potential to enhance antitumor effect. CPT-11 (Camptosar, irinotecan), a topoisomerase I inhibitor, has been shown to be highly effective in the treatment of a variety of cancers. However, its clinical usage is often complicated by late diarrhea. A number of studies have shown that cyclooxygenase (COX)-2 is overexpressed in many forms of human tumors, suggesting that COX-2 inhibition may be useful in the treatment of cancer. In this study, we used two mouse tumor models (HT-29 and colon-26 cells) to evaluate the effect of combining CPT-11 with celecoxib on tumor growth. We also assessed the involvement of COX-2 in the pathogenesis of CPT-11-induced late diarrhea using a rat model. Results indicate that celecoxib enhances the antitumor effect of CPT-11 and reduces the severity of late diarrhea in a dose-dependent manner. The extended benefits of combining celecoxib with CPT-11 may significantly improve the outcome of cancer patients.

Animals↗

Autonomic neural control of dynamic cerebral autoregulation in humans.

BACKGROUND: The purpose of the present study was to determine the role of autonomic neural control of dynamic cerebral autoregulation in humans. METHODS AND RESULTS: We measured arterial pressure and cerebral blood flow (CBF) velocity in 12 healthy subjects (aged 29+/-6 years) before and after ganglion blockade with trimethaphan. CBF velocity was measured in the middle cerebral artery using transcranial Doppler. The magnitude of spontaneous changes in mean blood pressure and CBF velocity were quantified by spectral analysis. The transfer function gain, phase, and coherence between these variables were estimated to quantify dynamic cerebral autoregulation. After ganglion blockade, systolic and pulse pressure decreased significantly by 13% and 26%, respectively. CBF velocity decreased by 6% (P<0.05). In the very low frequency range (0.02 to 0.07 Hz), mean blood pressure variability decreased significantly (by 82%), while CBF velocity variability persisted. Thus, transfer function gain increased by 81%. In addition, the phase lead of CBF velocity to arterial pressure diminished. These changes in transfer function gain and phase persisted despite restoration of arterial pressure by infusion of phenylephrine and normalization of mean blood pressure variability by oscillatory lower body negative pressure. CONCLUSIONS: These data suggest that dynamic cerebral autoregulation is altered by ganglion blockade. We speculate that autonomic neural control of the cerebral circulation is tonically active and likely plays a significant role in the regulation of beat-to-beat CBF in humans.

Adult↗

Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans.

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (< 0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.

Adult↗

Influence of microgravity on astronauts' sympathetic and vagal responses to Valsalva's manoeuvre.

When astronauts return to Earth and stand, their heart rates may speed inordinately, their blood pressures may fall, and some may experience frank syncope. We studied brief autonomic and haemodynamic transients provoked by graded Valsalva manoeuvres in astronauts on Earth and in space, and tested the hypothesis that exposure to microgravity impairs sympathetic as well as vagal baroreflex responses. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in four healthy male astronauts (aged 38-44 years) before, during and after the 16 day Neurolab space shuttle mission. Astronauts performed two 15 s Valsalva manoeuvres at each pressure, 15 and 30 mmHg, in random order. Although no astronaut experienced presyncope after the mission, microgravity provoked major changes. For example, the average systolic pressure reduction during 30 mmHg straining was 27 mmHg pre-flight and 49 mmHg in flight. Increases in muscle sympathetic nerve activity during straining were also much greater in space than on Earth. For example, mean normalized sympathetic activity increased 445% during 30 mmHg straining on earth and 792% in space. However, sympathetic baroreflex gain, taken as the integrated sympathetic response divided by the maximum diastolic pressure reduction during straining, was the same in space and on Earth. In contrast, vagal baroreflex gain, particularly during arterial pressure reductions, was diminished in space. This and earlier research suggest that exposure of healthy humans to microgravity augments arterial pressure and sympathetic responses to Valsalva straining and differentially reduces vagal, but not sympathetic baroreflex gain.

Adult↗