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Biomedical subjects

R L Hughson

Publications and source records attributed to R L Hughson.

At least 55 records · Page 3Linked to original sources

Prostaglandin inhibition causes an increase in reactive hyperaemia after ischaemic exercise in human forearm.

The hypothesis that prostaglandins contribute to the reactive hyperaemia after 5 min of ischaemia or 5 min of ischaemic exercise was investigated in six men by inhibiting prostaglandin production with ibuprofen (1800 mg) and indomethacin (225 mg) over 24 h before testing. Blood flow was measured continuously in the baseline and after ischaemia by combined pulsed and echo Doppler as the product of velocity and cross-sectional area. After 5 min of ischaemia, there were no differences in blood flow between placebo and the two drug conditions, except at 5 and 10 s when flow with indomethacin was greater than both placebo and ibuprofen. After 5 min of ischaemic exercise, blood flow was significantly greater as a consequence of increased vascular conductance in each of ibuprofen and indomethacin than placebo from 5 until 90 s of recovery. We conclude that prostaglandin inhibition had little or no effect on reactive hyperaemia after 5 min of circulatory occlusion alone, but that blood flow after ischaemic exercise was elevated due to increased vascular conductance when prostaglandin synthesis was inhibited.

Adult↗

Determination of baroreflex gain using auto-regressive moving-average analysis during spontaneous breathing.

The heart rate component of the arterial baroreflex gain (BRG) was determined with auto-regressive moving-average (ARMA) analysis during each of spontaneous (SB) and random breathing (RB) protocols. Ten healthy subjects completed each breathing pattern on two different days in each of two different body positions, supine (SUP) and head-up tilt (HUT). The R-R interval, systolic arterial pressure (SAP) and instantaneous lung volume were recorded continuously. BRG was estimated from the ARMA impulse response relationship of R-R interval to SAP and from the spontaneous sequence method. The results indicated that both the ARMA and spontaneous sequence methods were reproducible (r = 0.76 and r = 0.85, respectively). As expected, BRG was significantly less in the HUT compared to SUP position for both ARMA (mean +/- SEM; 3.5 +/- 0.3 versus 11.2 +/- 1.4 ms mmHg-1; P < 0.01) and spontaneous sequence analysis (10.3 +/- 0.8 versus 31.5 +/- 2.3 ms mmHg-1; P < 0.001). However, no significant difference was found between BRG during RB and SB protocols for either ARMA (7.9 +/- 1.4 versus 6.7 +/- 0.8 ms mmHg-1; P = 0.27) or spontaneous sequence methods (21.8 +/- 2.7 versus 20.0 +/- 2.1 ms mmHg-1; P = 0.24). BRG was correlated during RB and SB protocols (r = 0.80; P < 0.0001). ARMA and spontaneous BRG estimates were correlated (r = 0.79; P < 0.0001), with spontaneous sequence values being consistently larger (P < 0.0001). In conclusion, we have shown that ARMA-derived BRG values are reproducible and that they can be determined during SB conditions, making the ARMA method appropriate for use in a wider range of patients.

Adult↗

Cardiovascular dynamics at the onset of exercise.

At the onset of exercise, the cardiovascular system adapts with a series of integrated responses to meet the metabolic demands of the exercising muscles. The importance of rapid increases in cardiac output and local muscle blood flow has been established by showing that small decreases in O2 supply at the onset of exercise cause delays in the increase in O2 utilization. With the development of techniques that can be applied to instantaneous measurement of the cardiovascular response, the mechanisms that regulate increased muscle perfusion have recently been investigated. In this introduction to the symposium, a model of the within muscle distribution of blood flow is considered as a function of the measured responses across an exercising skeletal muscle. This model demonstrates the necessity of considering the distribution of blood flow to the working fibers very early in exercise. The symposium provides insight into our current understanding of the factors involved in the regulation of skeletal muscle blood flow at the onset of exercise. Our ability to study the impact of cardiovascular disease on exercise performance has improved with the development of selective pharmacological agents to block or stimulate specific components of the cardiovascular response. These advances should provide the basis for future research.

Adaptation, Physiological↗

Adaptation of blood flow during the rest to work transition in humans.

Beat-by-beat measurements show that limb blood flow rises rapidly and in a biphasic manner at the onset of rhythmic exercise in humans. In this review the time course of change in limb flow with the onset of exercise is described and the mechanisms that may or may not contribute to its regulation are discussed. The pumping action of contracting skeletal muscle appears to form an important regulator of increasing flow with the first contraction. However, evidence from human studies suggests that vasodilation begins with the first contraction. Whether this early dilation is regulated by neural recruitment of motor fibers and/or muscle contraction per se is discussed, but the mechanism(s) remains unclear. Finally, the contribution of endothelial-derived relaxation factors to the exponential increase in flow at the exercise onset is examined. Based on studies in humans with intra-arterial infusion of blocking drugs, neither acetylcholine, nitric oxide, nor prostaglandins appear to be essential for a normal dynamic flow response on going from rest to exercise. Overall, evidence from human studies supports the hypothesis that the rate of increase in blood flow during rhythmic voluntary exercise is closely coupled to motor unit recruitment with dilation beginning at the first contraction.

Adaptation, Physiological↗

Physical activity is a major contributor to the ultra low frequency components of heart rate variability.

OBJECTIVE: To investigate the link between changes in level of physical activity and the pattern of heart rate variability during long term ambulatory monitoring. DESIGN: Heart rate variability was measured simultaneously with a quantitative indicator of muscle activity by electromyography (EMG) in five men and five women while they did activities typical of daily life or while they rested for 2-3 hours. Spectral and cross spectral analyses were performed on both variables with standard fast Fourier transform. RESULTS: There was a marked reduction in spectral power in the ultra low frequency band (< 0.003 Hz) on going from active to rest conditions for both heart rate variability (men 6187 (1801) v 410 (89) ms(2)/Hz; women 4056 (1161) v 2094 (801), mean (SEM); p < 0.01) and EMG (p < 0.001). Cross spectral analysis showed a strong positive gain between the EMG and heart rate variability signal that was virtually eliminated in the resting condition (p < 0.01). A sex-by-condition effect (p = 0.06) was noted with a reduction in total spectral power for heart rate variability during rest in men, while it increased slightly in women. CONCLUSIONS: There is a quantitative link between muscle activation and heart rate variability in the lowest frequency band. Voluntary restriction of physical activity in healthy young subjects caused marked reduction in spectral power in the lowest frequency band which is often used to assess patient prognosis. The findings strongly suggest that studies of ambulatory heart rate variability should always include an indication of physical activity patterns.

Adult↗

Tissue oxygenation by near-infrared spectroscopy and muscle blood flow during isometric contractions of the forearm.

The relationship between tissue oxygenation measured by near-infrared spectroscopy (NIRS) and forearm muscle blood flow (FBF) measured by Doppler ultrasound was tested during isometric contractions at 10 and 30% maximal voluntary contraction (MVC) under conditions of normoxia and hypoxia (14% inspired O2). Six subjects maintained contractions at 10% MVC for 5 min and 30% for 2 min in both gas conditions. FBF was elevated during exercise at 10% MVC in hypoxia compared to normoxia, but there was no further increase in flow at 30% MVC. Median power frequency calculations from electromyographic recordings suggested progressive development of fatigue throughout both 10 and 30% MVC contractions. NIRS indicated no change in muscle oxygenation at 10% MVC, but deep venous blood O2 saturation was reduced in normoxia and more so in hypoxia. At 30% MVC, both NIRS and venous O2 saturation were reduced, with no effect of hypoxia on the NIRS signal. While NIRS might provide an indication of muscle oxygenation during isometric exercise, the conflicting findings for NIRS and direct venous blood sampling at 10 vs 30% MVC suggest caution in the application of this noninvasive technique.

Adult↗

Ischemic muscle chemoreflex response elevates blood flow in nonischemic exercising human forearm muscle.

We tested the hypothesis that forearm blood flow (FBF) might be reduced during forearm exercise when a vasoconstrictor response was evoked by calf exercise during calf ischemia (CE + I). In nine healthy subjects, brachial artery FBF and finger-cuff mean arterial pressure (MAP) were measured beat by beat during rest and forearm exercise. CE + I initiated before 5 min of forearm exercise (condition A) increased MAP by 24% and reduced resting forearm vascular conductance (FVC) by 24% such that FBF remained at the same level as without CE + I (control, condition C). With the onset of forearm exercise, the difference in FVC between condition A and condition C was abolished; consequently, the FBF adaptation to exercise was greater after 3 min of exercise in condition A (247.0 +/- 14.8 ml/min) than in condition C (197.1 +/- 9.4 ml/min, P < 0. 05) because of the elevated MAP. Gradual stimulation of the chemoreflex by the addition of CE + I at 3 min of a 9-min bout of forearm exercise (condition B) did not affect FVC such that progressive elevations in MAP resulted in proportional increases in FBF. We concluded that chemoreflex-mediated increases in systemic sympathetic nervous activity appear to affect resting FVC. Evidence from this study suggests that local factors responsible for initiating and maintaining vasodilation during moderate, small-muscle mass exercise can quickly override this vasoconstrictor influence such that FBF is elevated during exercise in direct proportion to the elevation in MAP.

Adaptation, Physiological↗

Comparison of femoral blood gases and muscle near-infrared spectroscopy at exercise onset in humans.

We hypothesized that near-infrared spectroscopy (NIRS) measures of hemoglobin and/or myoglobin O2 saturation (IR-SO2) in the vascular bed of exercising muscle would parallel changes in femoral venous O2 saturation (SfvO2) at the onset of leg-kicking exercise in humans. Six healthy subjects performed transitions from rest to 48 +/- 3 (SE)-W two-legged kicking exercise while breathing 14, 21, or 70% inspired O2. IR-SO2 was measured over the vastus lateralis muscle continuously during all tests, and femoral venous and radial artery blood samples were drawn simultaneously during rest and during 5 min of exercise. In all gas-breathing conditions, there was a rapid decrease in both IR-SO2 and SfvO2 at the onset of moderate-intensity leg-kicking exercise. Although SfvO2 remained at low levels throughout exercise, IR-SO2 increased significantly after the first minute of exercise in both normoxia and hyperoxia. Contrary to the hypothesis, these data show that NIRS does not provide a reliable estimate of hemoglobin and/or O2 saturation as reflected by direct femoral vein sampling.

Adult↗

Interaction of factors determining oxygen uptake at the onset of exercise.

Considerable debate surrounds the issue of whether the rate of adaptation of skeletal muscle O2 consumption (QO2) at the onset of exercise is limited by 1) the inertia of intrinsic cellular metabolic signals and enzyme activation or 2) the availability of O2 to the mitochondria, as determined by an extrinsic inertia of convective and diffusive O2 transport mechanisms. This review critically examines evidence for both hypotheses and clarifies important limitations in the experimental and theoretical approaches to this issue. A review of biochemical evidence suggests that a given respiratory rate is a function of the net drive of phosphorylation potential and redox potential and cellular mitochondrial PO2 (PmitoO2). Changes in both phosphorylation and redox potential are determined by intrinsic metabolic inertia. PmitoO2 is determined by the extrinsic inertia of both convective and diffusive O2 transport mechanisms during the adaptation to exercise and the rate of mitochondrial O2 utilization. In a number of exercise conditions, PmitoO2 appears to be within a range capable of modulating muscle metabolism. Within this context, adjustments in the phosphate energy state of the cell would serve as a cytosolic "transducer," linking ATP consumption with mitochondrial ATP production and, therefore, O2 consumption. The availability of reducing equivalents and O2 would modulate the rate of adaptation of QO2.

Animals↗

Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest.

Cardiovascular responses to orthostatic tests were studied before and after a prolonged 42 day-head-down bed-rest (HDBR;-6 degrees) experiment simulating a long duration space flight. Seven men participating in the experiment underwent stand tests (10 min) and lower body negative pressure (LBNP) tests (5 min at -25, -35, -45 mmHg). Heart rate variability and spontaneous baroreflex response slope (SBS) were analysed to assess autonomic nervous system responses. Changes in plasma volume (PV) were assessed at the end of HDBR. At the end of HDBR, four subjects could not complete the stand tests and one could not complete the LBNP test. A higher stressed heart rate with standing (+ 44% before and + 57% after HDBR) and LBNP exposure (+ 19% before and + 34% after HDBR) were observed. A decrease in blood pressure (BP) reflecting a reduced vasomotor response was only observed with standing (mean BP + 21% before and -8% after HDBR); LBNP was less sensitive probably because it was performed 6 h after the stand test. The PV decreased by 10.6%. A decline in spectrum total power reflecting a reduced variance of RR-interval, a decrease in parasympathetic activity and an increase in sympathetic one were observed at the end of HDBR. The reduced parasympathetic indicator and SBS would suggest that the vagal nerve component of the cardiovascular control had been diminished. Except for a lower BP when standing after HDBR, no significant difference was observed between finishers and non-finishers. Autonomic nervous system changes including reduced vasomotor responses constituted important contributors to the orthostatic intolerance observed here and after space flights. Some autonomic and PV changes seemed to be opposite to those observed with training and would suggest a role of reduced physical activity in cardiovascular changes induced by HDBR.

Adult↗

Vasodilation contributes to the rapid hyperemia with rhythmic contractions in humans.

The hypothesis that the rapid increases in blood flow at the exercise onset are exclusively due to the mechanical effects of the muscle pump was tested in six volunteers during dynamic handgrip exercise. While supine, each subject completed a series of eight different exercise tests in which brachial artery blood pressure (BP) was altered by 25-30 mmHg (1 mmHg = 133.3 Pa) by positioning the arm above or below the heart. Two different weights, corresponding to 4.9 and 9.7% of maximal voluntary isometric contraction, were raised and lowered at two different contraction rate schedules (1s:1s and 2s:2s work-rest) each with a 50% duty cycle. Beat-by-beat measures of mean blood velocity (MBV) (pulsed Doppler) were obtained at rest and for 5 min following step increases in work rate with emphasis on the first 24 s. MBV was increased 50-100% above rest following the first contraction in both arm positions (p < 0.05). The increase in MBV from rest was greater in the below position compared with above, and this effect was observed following the first and subsequent contractions (p < 0.05). However, the positional effect on the increase in MBV could not be explained entirely by the approximately 40% greater BP in this position. Also, the greater workload resulted in greater increases in MBV as early as the first contraction, compared with the light workload (p < 0.05) despite similar reductions in forearm volume following single contractions. MBV was greater with faster contraction rate tests by 8 s of exercise. It was concluded that microvascular vasodilation must act in concert with a reduction in venous pressure to increase forearm blood flow within the initial 2-4 s of exercise.

Adult↗

Changes in the sympathetic nervous system induced by 42 days of head-down bed rest.

Changes in autonomic nervous system activity could be linked to the orthostatic intolerance (OI) that individuals suffer after a spaceflight or head-down bed rest (HDBR). We examined this possibility by assessing the sympathetic nervous system activity during 42 days of HDBR in seven healthy men. Heart rate variability was studied with the use of power spectral analysis, which provided indicators of the sympathetic (SNSi) and parasympathetic (PNSi) nervous system influences on the heart. Urinary catecholamines and the spontaneous baroreflex sensitivity were measured. Urinary catecholamines decreased by 21.3%, showing a decrease in SNSi. Heart rate variability was greatly reduced during 42 days of HDBR with a drop in PNSi but with no significant changes in SNSi. The baroreflex sensitivity was greatly reduced (30.7%) on day 42 of HDBR. These results suggest a dissociation between the catecholamine response and the SNSi of the heart rate. This dissociation could be the consequence of an increase in beta-adrenergic receptor density and/or activity induced by a decrease in catecholamines during HDBR. The subjects who suffered from OI also had a greater sympathetic response and much lower baroreflex sensitivity when supine than those who finished the stand test. However, the mean response of all subjects indicated that the sympathetic activity (catecholamine excretion) was probably slightly inhibited during HDBR and could contribute to OI.

Adult↗

Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans.

We tested the hypothesis that the slower increase in alveolar oxygen uptake (VO2) at the onset of supine, compared with upright, exercise would be accompanied by a slower rate of increase in leg blood flow (LBF). Seven healthy subjects performed transitions from rest to 40-W knee extension exercise in the upright and supine positions. LBF was measured continuously with pulsed and echo Doppler methods, and VO2 was measured breath by breath at the mouth. At rest, a smaller diameter of the femoral artery in the supine position (P < 0. 05) was compensated by a greater mean blood flow velocity (MBV) (P < 0.05) so that LBF was not different in the two positions. At the end of 6 min of exercise, femoral artery diameter was larger in the upright position and there were no differences in VO2, MBV, or LBF between upright and supine positions. The rates of increase of VO2 and LBF in the transition between rest and 40 W exercise, as evaluated by the mean response time (time to 63% of the increase), were slower in the supine [VO2 = 39.7 +/- 3.8 (SE) s, LBF = 27.6 +/- 3.9 s] than in the upright positions (VO2 = 29.3 +/- 3.0 s, LBF = 17.3 +/- 4.0 s; P < 0.05). These data support our hypothesis that slower increases in alveolar VO2 at the onset of exercise in the supine position are accompanied by a slower increase in LBF.

Adult↗

Kinetics of oxygen uptake at the onset of exercise in boys and men.

The objective of this study was to compare the O2 uptake (VO2) kinetics at the onset of heavy exercise in boys and men. Nine boys, aged 9-12 yr, and 8 men, aged 19-27 yr, performed a continuous incremental cycling task to determine peak VO2 (VO2 peak). On 2 other days, subjects performed each day four cycling tasks at 80 rpm, each consisting of 2 min of unloaded cycling followed twice by cycling at 50% VO2 peak for 3.5 min, once by cycling at 100% VO2 peak for 2 min, and once by cycling at 130% VO2 peak for 75 s. O2 deficit was not significantly different between boys and men (respectively, 50% VO2 peak task: 6.6 +/- 11.1 vs. 5.5 +/- 7.3 ml . min-1 . kg-1; 100% VO2 peak task: 28.5 +/- 8.1 vs. 31.8 +/- 6.3 ml . min-1 . kg-1; and 130% VO2 peak task: 30.1 +/- 5.7 vs. 35.8 +/- 5.3 ml . min-1 . kg-1). To assess the kinetics, phase I was excluded from analysis. Phase II VO2 kinetics could be described in all cases by a monoexponential function. ANOVA revealed no differences in time constants between boys and men (respectively, 50% VO2 peak task: 22. 8 +/- 5.1 vs. 26.4 +/- 4.1 s; 100% VO2 peak task: 28.0 +/- 6.0 vs. 28.1 +/- 4.4 s; and 130% VO2 peak task: 19.8 +/- 4.1 vs. 20.7 +/- 5. 7 s). In conclusion, O2 deficit and fast-component VO2 on-transients are similar in boys and men, even at high exercise intensities, which is in contrast to the findings of other studies employing simpler methods of analysis. The previous interpretation that children rely less on nonoxidative energy pathways at the onset of heavy exercise is not supported by our findings.

Adult↗

Effects of acetylcholine and nitric oxide on forearm blood flow at rest and after a single muscle contraction.

We tested the hypothesis that ACh or nitric oxide (NO) might be involved in the vasodilation that accompanies a single contraction of the forearm. Eight adults (3 women and 5 men) completed single 1-s-duration contractions of the forearm to raise and lower a weight equivalent to approximately 20% maximal voluntary contraction through a distance of 5 cm. In a second protocol, each subject had a cuff, placed completely about the forearm, inflated to 120 mmHg for a 1-s period, then released as a simulation of the mechanical effect of muscle contraction. Three conditions were studied, always in this order: 1) control, with intra-arterial infusion of saline; 2) after muscarinic blockade with atropine; and 3) after NO synthase inhibition with NG-monomethyl-L-arginine (L-NMMA) plus atropine. Forearm blood flow (FBF), measured by combined pulsed and echo Doppler ultrasound, was reduced at rest with L-NMMA-atropine compared with the other two conditions. After the single contraction, there were no effects of atropine, but L-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereas L-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation that L-NMMA reduced FBF in response to both cuff inflation and a brief contraction indicates that NO from the vascular endothelium might modulate the basal level of vascular tone and the mechanical component of the hyperemia with exercise. It is unlikely that ACh and NO from the endothelium are involved in the dilator response to a single muscle contraction.

Acetylcholine↗

Respiratory influences on non-linear dynamics of heart rate variability in humans.

The goal of our study was to determine whether evidence for chaos in heart rate variability (HRV) can be observed when the respiratory input to the autonomic controller of heart rate is forced by the deterministic pattern associated with periodic breathing. We simultaneously recorded, in supine healthy volunteers, RR intervals and breathing volumes for 20 to 30 min (1024 data point series) during three protocols: rest (control), fixed breathing (15 breath/min) and voluntary periodic breathing (3 breaths with 2 s inspiration and 2 s expiration followed by an 8 s breath hold). On both the RR interval and breathing volume series we applied the non-linear prediction method (Sugihara and May algorithm) to the original time series and to distribution-conserved isospectral surrogate data. Our results showed that, in contrast to the control test, during both fixed and voluntary periodic breathing the variability of breathing volumes was clearly deterministic non-chaotic. During all the three protocols, the RR-interval series' non-linear predictability was consistent with one of a chaotic series. However, at rest, no clear difference was observed between the RR-interval series and their surrogates, which means that no clear chaos was observed. During fixed breathing a difference appeared, and this difference seemed clearer during voluntary periodic breathing. We concluded that HRV dynamics were chaotic when respiration was forced with a deterministic non-chaotic pattern and that normal spontaneous respiratory influences might mask the normally chaotic pattern in HRV.

Adult↗