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Biomedical subjects

James A Pawelczyk

Publications and source records attributed to James A Pawelczyk.

9 recordsLinked to original sources
PubMed2026

Network oscillatory dynamics accompany cerebral bioenergetic defence in hypoxia.

A network physiology framework investigated how coordinated interactions among multiple organ systems collectively support the preservation of cerebral bioenergetic function and better distinguish adaptive from maladaptive responses to hypoxia. Twelve healthy males were passively exposed to 6 h of normoxia (21% O2) and hypoxia (12% O2) in a randomised, single-blind, crossover design. Venous blood was assayed for oxidative-nitrosative stress (OXNOS, spectroscopy/chemiluminescence) and neurovascular unit (hs-ELISA) biomarkers. Global cerebral delivery of O2 and glucose were determined by duplex ultrasound. Clinical acute mountain sickness (AMS+) was diagnosed in five participants. Cerebral substrate delivery was well maintained in both hypoxia and AMS+ (p < 0.05 vs normoxia and AMS-) despite marked arterial hypoxemia. Bioenergetic defence coincided with pronounced elevations in the spectral amplitude and phase synchronisation of very low-frequency oscillations (VLFOs, 0.03-0.06 Hz), which were evident across multiple organ systems and most prominent within the cerebral network. Systemic VLFOs were further exaggerated and more functionally connected in AMS+ in the absence of exaggerated systemic OXNOS or structural damage/destabilisation of the neurovascular unit (both p < 0.05 vs normoxia and AMS-). Collectively, these findings suggest that AMS, while characterised by debilitating symptomatology, may reflect a neuroprotective adaptive as opposed to pathologically maladaptive phenotype.

Humans↗
PubMed2006

Human cerebral autoregulation before, during and after spaceflight.

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased significantly (P < 0.05) by 26, 23 and 27% after 1 and 2 weeks in space and on landing day, respectively, compared with preflight values, which is also consistent with improved autoregulation. We conclude that human cerebral autoregulation is preserved, and possibly even improved, by short-duration spaceflight.

Adaptation, Physiological↗
PubMed2006

Evidence for reduced sympatholysis in leg resistance vasculature of healthy older women.

Inhibition of a sympathetic stimulus (i.e., sympatholysis) during forearm exercise is reduced with age in women. This age-related alteration has not been characterized in the lower extremity vasculature of women, and the potential for blunting of the conduit artery dilatory response to a sudden increase in shear stress [flow-mediated dilation (FMD)] has not been examined in older adults of either sex. In the present study, we assessed popliteal artery diameter and velocity (Doppler ultrasound) in 16 young (23 +/- 1 yr) and 14 older (69 +/- 1 yr) women after 5 min of distal calf occlusion (FMD), 3 min of hand immersion in ice water [cold pressor test (CPT)], and 5 min of distal calf occlusion combined with hand immersion in ice water (FMD+CPT). Peak popliteal conductance after 5-min ischemia was not significantly different in young vs. older women. During the combined stimulus (FMD+CPT), the magnitude of vasoconstriction in the calf (reduction in peak popliteal artery conductance) was similar (5-8%), despite reduced resting adrenergic sensitivity to CPT [young (Y): -27.3 +/- 3.8%; older (O): -15.8 +/- 2.2%; P < 0.05] and blunted muscle sympathetic nerve activity responses to CPT (Y: 12.7 +/- 3.6 bursts/min; O: 7.8 +/- 2.5 bursts/min; P < 0.05) in older women. Popliteal FMD, normalized to the shear stimulus, was attenuated by 60-70% in older women. Peak popliteal diameter, measured during the combined stimulus (FMD+CPT), was blunted in young but not in older women (Y FMD: 5.5 +/- 0.1 mm; Y FMD+CPT: 5.4 +/- 0.1 mm; P = 0.03; O FMD: 5.8 +/- 0.2 mm; O FMD+CPT: 5.8 +/- 0.2 mm). These results confirm previous findings of diminished reactivity in the conduit arteries of older humans and provide the first evidence of reduced sympatholysis in the leg resistance vasculature of older women.

Administration, Sublingual↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

Human muscle sympathetic neural and haemodynamic responses to tilt following spaceflight.

Orthostatic intolerance is common when astronauts return to Earth: after brief spaceflight, up to two-thirds are unable to remain standing for 10 min. Previous research suggests that susceptible individuals are unable to increase their systemic vascular resistance and plasma noradrenaline concentrations above pre-flight upright levels. In this study, we tested the hypothesis that adaptation to the microgravity of space impairs sympathetic neural responses to upright posture on Earth. We studied six astronauts approximately 72 and 23 days before and on landing day after the 16 day Neurolab space shuttle mission. We measured heart rate, arterial pressure and cardiac output, and calculated stroke volume and total peripheral resistance, during supine rest and 10 min of 60 deg upright tilt. Muscle sympathetic nerve activity was recorded in five subjects, as a direct measure of sympathetic nervous system responses. As in previous studies, mean (+/- S.E.M.) stroke volume was lower (46 +/- 5 vs. 76 +/- 3 ml, P = 0.017) and heart rate was higher (93 +/- 1 vs. 74 +/- 4 beats min(-1), P = 0.002) during tilt after spaceflight than before spaceflight. Total peripheral resistance during tilt post flight was higher in some, but not all astronauts (1674 +/- 256 vs. 1372 +/- 62 dynes s cm(-5), P = 0.32). No crew member exhibited orthostatic hypotension or presyncopal symptoms during the 10 min of postflight tilting. Muscle sympathetic nerve activity was higher post flight in all subjects, in supine (27 +/- 4 vs. 17 +/- 2 bursts min(-1), P = 0.04) and tilted (46 +/- 4 vs. 38 +/- 3 bursts min(-1), P = 0.01) positions. A strong (r(2) = 0.91-1.00) linear correlation between left ventricular stroke volume and muscle sympathetic nerve activity suggested that sympathetic responses were appropriate for the haemodynamic challenge of upright tilt and were unaffected by spaceflight. We conclude that after 16 days of spaceflight, muscle sympathetic nerve responses to upright tilt are normal.

Adult↗
PubMed2002

Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space.

Astronauts returning from space have reduced red blood cell masses, hypovolaemia and orthostatic intolerance, marked by greater cardio-acceleration during standing than before spaceflight, and in some, orthostatic hypotension and presyncope. Adaptation of the sympathetic nervous system occurring during spaceflight may be responsible for these postflight alterations. We tested the hypotheses that exposure to microgravity reduces sympathetic neural outflow and impairs sympathetic neural responses to orthostatic stress. We measured heart rate, photoplethysmographic finger arterial pressure, peroneal nerve muscle sympathetic activity and plasma noradrenaline spillover and clearance, in male astronauts before, during (flight day 12 or 13) and after the 16 day Neurolab space shuttle mission. Measurements were made during supine rest and orthostatic stress, as simulated on Earth and in space by 7 min periods of 15 and 30 mmHg lower body suction. Mean (+/- S.E.M.) heart rates before lower body suction were similar pre-flight and in flight. Heart rate responses to -30 mmHg were greater in flight (from 56 +/- 4 to 72 +/- 4 beats min(-1)) than pre-flight (from 56 +/- 4 at rest to 62 +/- 4 beats min(-1), P < 0.05). Noradrenaline spillover and clearance were increased from pre-flight levels during baseline periods and during lower body suction, both in flight (n = 3) and on post-flight days 1 or 2 (n = 5, P < 0.05). In-flight baseline sympathetic nerve activity was increased above pre-flight levels (by 10-33 %) in the same three subjects in whom noradrenaline spillover and clearance were increased. The sympathetic response to 30 mmHg lower body suction was at pre-flight levels or higher in each subject (35 pre-flight vs. 40 bursts min(-1) in flight). No astronaut experienced presyncope during lower body suction in space (or during upright tilt following the Neurolab mission). We conclude that in space, baseline sympathetic neural outflow is increased moderately and sympathetic responses to lower body suction are exaggerated. Therefore, notwithstanding hypovolaemia, astronauts respond normally to simulated orthostatic stress and are able to maintain their arterial pressures at normal levels.

Adult↗
PubMed2002

Heterogeneous responses of human limbs to infused adrenergic agonists: a gravitational effect?

Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures relative to the arms. We hypothesized that this "dependent hypertension" would be associated with altered adrenergic responsiveness. Isoproterenol (0.75-24 ng x 100 ml limb volume-1 x min-1) and phenylephrine (0.025-0.8 microg x 100 ml limb volume-1 x min-1) were infused incrementally in the brachial and femoral arteries of 12 normal volunteers; changes in limb blood flow were quantified by using strain-gauge plethysmography. Compared with the forearm, baseline calf vascular resistance was greater (38.8 +/- 2.5 vs. 26.9 +/- 2.0 mmHg x 100 ml x min x ml-1; P < 0.001) and maximal conductance was lower (46.1 +/- 11.9 vs. 59.4 +/- 13.4 ml x ml-1 x min-1 x mmHg-1; P < 0.03). Vascular conductance did not differ between the two limbs during isoproterenol infusions, whereas decreases in vascular conductance were greater in the calf than the forearm during phenylephrine infusions (P < 0.001). With responses normalized to maximal conductance, the half-maximal response for phenylephrine was significantly less for the calf than the forearm (P < 0.001), whereas the half-maximal response for isoproterenol did not differ between limbs. We conclude that alpha1- but not beta-adrenergic-receptor responsiveness in human limbs is nonuniform. The relatively greater response to alpha1-adrenergic-receptor stimulation in the calf may represent an adaptive mechanism that limits blood pooling and capillary filtration in the legs during standing.

Adaptation, Physiological↗