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Biomedical subjects

Richard L Hughson

Publications and source records attributed to Richard L Hughson.

16 recordsLinked to original sources

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.

Aged↗

Effect of acute sympathetic nervous system activation on flow-mediated dilation of brachial artery.

We tested the hypothesis that flow-mediated dilation (FMD) of the brachial artery would be impaired by acute increases in sympathetic nervous system activity (SNA) in models where similar peak shear stress stimulus was achieved by varying the duration of forearm muscle ischemia. Eleven healthy young men were studied under four different conditions, each with its own control: lower body suction (LBS), cold pressor test (CPT), mental arithmetic task (MAT), and activation of muscle chemoreflex (MCR). The duration of ischemia before observation of FMD by ultrasound imaging was 5 min each for control, LBS, and CPT; 3 min for MAT; and 2-min for MCR. Peak shear rate was not different between control and any of the SNA conditions, although total shear in the first minute was reduced in MAT. MCR was the only condition in which brachial artery vasoconstriction was observed before forearm occlusion [4.38 (SD 0.53) vs. control 4.60 (SD 0.53) mm, P < 0.05]; however, diameter increased to the same absolute value as that of the control, so the percent FMD was greater for MCR [9.85 (SD 2.33) vs. control 5.29 (SD 1.50)%]. Blunting of the FMD response occurred only in the CPT model [1.51 (SD 1.20)%]. During SNA, the increase in plasma cortisol from baseline was significant only for MCR; the increase in plasma norepinephrine was significant for MCR, LBS, and CPT; and the increase in epinephrine was significant only for MCR. These results showed that the four models employed to achieve increases in SNA had different effects on baseline brachial artery diameter and that blunted FMD is not a general response to increased SNA.

Adult↗

Oxygen uptake kinetics are slowed in cystic fibrosis.

PURPOSE: There are conflicting reports on the kinetics of oxygen uptake at the onset of exercise in patients with cystic fibrosis (CF). The objective of the present study was, therefore, to compare oxygen uptake (VO(2) kinetics in patients with CF with those of healthy controls (CON). METHODS: Eighteen CF patients (FEV1 37-98% predicted) and 15 CON aged 10-33 yr completed two to four transitions from low-intensity cycling (stage 1, 20 W) to cycling at 1.3-1.4 W.kg(-1) body weight (stage 2). There was no difference between groups in heart rate at stages 1 and 2 or in relative exercise intensity, as expressed as percent VO(2peak) or percentage of ventilatory threshold. However, oxygen saturation (SpO(2)) was lower in the patients with CF during both stages. VO(2) data were interpolated second by second, time-aligned, and averaged. Monoexponential equations were used to describe phase II VO(2) responses. RESULTS: Although there were no differences between CF and CON in amplitude (10.9 +/- 1.8 vs 10.2 +/- 1.6 mL O2.W(-1)) of phase II VO(2) response, the time constant tau was significantly prolonged in CF compared with CON (36.8 +/- 13.6 vs 26.4 +/- 9.1 s). When tau was adjusted for the effects of FEV1 or SpO(2) during submaximal exercise, the difference between CF patients and controls disappeared. CONCLUSION: VO(2) kinetics are slowed in CF, which may, in part, be attributed to an impairment of oxygen delivery.

Adolescent↗

Feedback effects of circulating norepinephrine on sympathetic outflow in healthy subjects.

The amplitude of low-frequency (LF) oscillations of heart rate (HR) usually reflects the magnitude of sympathetic activity, but during some conditions, e.g., physical exercise, high sympathetic activity results in a paradoxical decrease of LF oscillations of HR. We tested the hypothesis that this phenomenon may result from a feedback inhibition of sympathetic outflow caused by circulating norepinephrine (NE). A physiological dose of NE (100 ng.kg(-1).min(-1)) was infused into eight healthy subjects, and infusion was continued after alpha-adrenergic blockade [with phentolamine (Phe)]. Muscle sympathetic nervous activity (MSNA) from the peroneal nerve, LF (0.04-0.15 Hz) and high frequency (HF; 0.15-0.40 Hz) spectral components of HR variability, and systolic blood pressure variability were analyzed at baseline, during NE infusion, and during NE infusion after Phe administration. The NE infusion increased the mean blood pressure and decreased the average HR (P < 0.01 for both). MSNA (10 +/- 2 vs. 2 +/- 1 bursts/min, P < 0.01), LF oscillations of HR (43 +/- 13 vs. 35 +/- 13 normalized units, P < 0.05), and systolic blood pressure (3.1 +/- 2.3 vs. 2.0 +/- 1.1 mmHg2, P < 0.05) decreased significantly during the NE infusion. During the NE infusion after PHE, average HR and mean blood pressure returned to baseline levels. However, MSNA (4 +/- 2 bursts/min), LF power of HR (33 +/- 9 normalized units), and systolic blood pressure variability (1.7 +/- 1.1 mmHg2) remained significantly (P < 0.05 for all) below baseline values. Baroreflex gain did not change significantly during the interventions. Elevated levels of circulating NE cause a feedback inhibition on sympathetic outflow in healthy subjects. These inhibitory effects do not seem to be mediated by pressor effects on the baroreflex loop but perhaps by a presynaptic autoregulatory feedback mechanism or some other mechanism that is not prevented by a nonselective alpha-adrenergic blockade.

Adolescent↗

Spontaneous beat-by-beat fluctuations of total peripheral and cerebrovascular resistance in response to tilt.

Beat-by-beat estimates of total peripheral resistance (TPR) can be obtained from continuous measurements of cardiac output by using Doppler ultrasound and noninvasive mean arterial blood pressure (MAP). We employed transfer function analysis to study the heart rate (HR) and vascular response to spontaneous changes in blood pressure from the relationships of systolic blood pressure (SBP) to HR (SBP-->HR), MAP to total peripheral resistance (TPR) and cerebrovascular resistance index (CVRi) (MAP-->TPR and MAP-->CVRi), as well as stroke volume (SV) to TPR in nine healthy subjects in supine and 45 degrees head-up tilt positions. The gain of the SBP-->HR transfer function was reduced with tilt in both the low- (0.03-0.15 Hz) and high-frequency (0.15-0.35 Hz) regions. In contrast, MAP-->TPR transfer function gain was not affected by head-up tilt, but it did increase from low- to high-frequency regions. The phase relationships between MAP-->TPR were unaffected by head-up tilt, but, consistent with an autoregulatory system, changes in MAP were followed by directionally similar changes in TPR, just as observed for the MAP-->CVRi. The SV-->TPR had high coherence with a constant phase of 150-160 degrees. Together, these data that showed changes in MAP preceded changes in TPR, as well as a possible link between SV and TPR, are consistent with complex interactions between the vascular component of the arterial and cardiopulmonary baroreflexes and intrinsic properties such as the myogenic response of the resistance arteries.

Adult↗

Two-breath CO(2) test detects altered dynamic cerebrovascular autoregulation and CO(2) responsiveness with changes in arterial P(CO(2)).

The new two-breath CO(2) method was employed to test the hypotheses that small alterations in arterial P(CO(2)) had an impact on the magnitude and dynamic response time of the CO(2) effect on cerebrovascular resistance (CVRi) and the dynamic autoregulatory response to fluctuations in arterial pressure. During a 10-min protocol, eight subjects inspired two breaths from a bag with elevated P(CO(2)), four different times, while end-tidal P(CO(2)) was maintained at three levels: hypocapnia (LoCO(2), 8 mmHg below resting values), normocapnia, and hypercapnia (HiCO(2), 8 mmHg above resting values). Continuous measurements were made of mean blood pressure corrected to the level of the middle cerebral artery (BP(MCA)), P(CO(2)) (estimated from expired CO(2)), and mean flow velocity (MFV, of the middle cerebral artery by Doppler ultrasound), with CVRi = BP(MCA)/MFV. Data were processed by a system identification technique (autoregressive moving average analysis) with gain and dynamic response time of adaptation estimated from the theoretical step responses. Consistent with our hypotheses, the magnitude of the P(CO(2))-CVRi response was reduced from LoCO(2) to HiCO(2) [from -0.04 (SD 0.02) to -0.01 (SD 0.01) (mmHg x cm(-1) x s) x mmHg Pco(2)(-1)] and the time to reach 95% of the step plateau increased from 12.0 +/- 4.9 to 20.5 +/- 10.6 s. Dynamic autoregulation was impaired with elevated P(CO(2)), as indicated by a reduction in gain from LoCO(2) to HiCO(2) [from 0.021 +/- 0.012 to 0.007 +/- 0.004 (mmHg x cm(-1) x s) x mmHg BP(MCA)(-1)], and time to reach 95% increased from 3.7 +/- 2.8 to 20.0 +/- 9.6 s. The two-breath technique detected dependence of the cerebrovascular CO(2) response on P(CO(2)) and changes in dynamic autoregulation with only small deviations in estimated arterial P(CO(2)).

Adult↗

Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions.

Different magnitudes and durations of postocclusion reactive hyperemia were achieved by occluding different volumes of tissue with and without ischemic exercise to test the hypotheses that flow-mediated dilation (FMD) of the brachial artery would depend on the increase in peak flow rate or shear stress and that the position of the occlusion cuff would affect the response. The brachial artery FMD response was observed by high-frequency ultrasound imaging with curve fitting to minimize the effects of random measurement error in eight healthy, young, nonsmoking men. Reactive hyperemia was graded by 5-min occlusion distal to the measurement site at the wrist and the forearm and proximal to the site in the upper arm. Flow was further increased by exercise during occlusion at the wrist and forearm positions. For the two wrist occlusion conditions, flow increased eightfold and FMD was only 1 to 2% (P > 0.05). After the forearm and upper arm occlusions, blood flow was almost identical but FMD after forearm occlusions was 3.4% (P < 0.05), whereas it was significantly greater (6.6%, P < 0.05) and more prolonged after proximal occlusion. Forearm occlusion plus exercise caused a greater and more prolonged increase in blood flow, yet FMD (7.0%) was qualitatively and quantitatively similar to that after proximal occlusion. Overall, the magnitude of FMD was significantly correlated with peak forearm blood flow (r = 0.59, P < 0.001), peak shear rate (r = 0.49, P < 0.002), and total 5-min reactive hyperemia (r = 0.52, P < 0.001). The prolonged FMD after upper arm occlusion suggests that the mechanism for FMD differs with occlusion cuff position.

Adult↗

The effect of prolonged submaximal exercise on gas exchange kinetics and ventilation during heavy exercise in humans.

This study compared ventilation, gas exchange (oxygen uptake, VO(2)) and the surface electromyogram (EMG) activity of four major lower limb muscles during heavy exercise before (Pre-Ex) and after (Post-Ex) a sustained 90-min cycling exercise at 60% VO(2peak). The 90-min exercise was incorporated under the hypothesis that sustained exercise would alter substrate availability in the second exercise bout causing differences in fibre recruitment patterns, gas exchange and ventilation. Nine trained male subjects [VO(2peak)=60.2 (1.7) ml.kg(-1).min(-1)] completed two identical 6-min bouts of cycling performed at high intensity [approximately 90% VO(2peak); 307 (6) W, mean (SE)]. Ventilation and gas exchange were measured breath-by-breath and the EMG was recorded during the last 12 s of each minute of the two 6-min bouts. EMG signals were analysed to determine integrated EMG (iEMG) and mean power frequency (MPF). VO(2) at min 3 and min 6 in Post-Ex were significantly higher (i.e., +201 and 141 ml.min(-1), respectively, P<0.05) than in Pre-Ex but there was a approximately 25% decrease of the slow component, taken as the difference between min 6 and min 3 [187 (27) vs 249 (35) ml.min(-1), respectively, P<0.05]. The greater whole-body VO(2) after 3 min of exercise in Post-Ex was not accompanied by clear alterations in the iEMG and MPF of the examined leg muscles. Ventilation and heart rate were elevated (approximately 12-16 l.min(-1) and approximately 10 beats.min(-1), respectively, P<0.05) as were the ratios V(E)/O(2) and V(E)/VCO(2) in the Post-Ex tests. It was concluded that the VO(2) and ventilation responses to high-intensity exercise can be altered following prolonged moderate intensity exercise in terms of increased amplitude without associated major changes in either iEMG or MPF values among conditions.

Adult↗

Effects of aerobic training on heart rate dynamics in sedentary subjects.

This study was designed to assess the effects of moderate- and high-volume aerobic training on the time domain and on spectral and fractal heart rate (HR) variability indexes. Sedentary subjects were randomized into groups with moderate-volume training (n = 20), high-volume training (n = 20), and controls (n = 15). The training period was 8 wk, including 6 sessions/wk at an intensity of 70-80% of the maximum HR, lasting for 30 min/session in the moderate-volume group and 60 min/session in the high-volume group. Time domain, frequency domain, and short-term fractal scaling measures of HR variability were analyzed over a 24-h period. Mean HR decreased from 70 +/- 7 to 64 +/- 8 beats/min and from 67 +/- 5 to 60 +/- 6 beats/min (P < 0.001 for both) for the moderate- and high-volume training groups, respectively. The normalized high-frequency spectral component increased in both groups (P < 0.05). The normalized low-frequency component decreased significantly (P < 0.05), resulting in a marked decrease in low frequency-to-high frequency ratio in both groups. In addition, short-term scaling exponent decreased in both groups (P < 0.001). There were no significant differences in the changes of HR variability indexes between groups. Aerobic training in sedentary subjects results in altered autonomic regulation of HR toward vagal dominance. A moderate training volume is a sufficient intervention to induce these beneficial effects.

Adult↗

Blunted cardiac autonomic responsiveness to hypoxemic stress in healthy older adults.

Supine resting cardiac dynamics and responses to steady-state hypoxemia were investigated in six healthy older (59-72 yrs) adults using coarse-graining spectral analysis of heart rate variability (HRV) and were compared to six young (22-29 yrs) adults studied previously (Lucy et al., 2000). End-tidal carbon dioxide pressure (PETCO2) was clamped at 1-2 mmHg above the usual resting value for 11 min of euoxia (PETO2 100 mmHg), followed by 22 min of hypoxia (PETO2 55 mmHg). During euoxia, vagally mediated harmonic and fractal power of HRV of older adults was minimal. Hypoxia induced an increase in ventilation, p < 0.01, and heart rate, p < 0.05. The heart rate increase (mean +/- SE) of 0.23 +/- 0.08 beats.min-1 per 1% decrease in arterial O2 saturation was 25% of that demonstrated previously by young subjects, p < 0.001. In older adults, HRV spectral power remained unchanged during hypoxia, providing further evidence of an age-related blunting of cardiac autonomic function.

Aged↗

Regulation of blood flow at the onset of exercise by feed forward and feedback mechanisms.

Blood flow adapts quickly after the onset of exercise to meet the metabolic demands of skeletal muscle. This review approaches the issue of how rapidly blood flow adapts and what the mechanisms for adaptation are primarily from a control theory perspective. Several recent papers have suggested that O2 transport proceeds at a rate that anticipates the metabolic demand over a very wide range of work rates. When considered from a control theory perspective, this implies involvement of feed forward control. Although there is one very important feed forward mechanism in the muscle pump that is activated with the onset of exercise, other evidence suggests that adjustment of blood flow to match the metabolic demand relies on feedback control from local dilator factors released in proportion to the metabolic demand. These distinct mechanisms with different onset times mean that blood flow adapts to the exercise demand with at least two distinct phases. The time course of the adaptation varies greatly between work rates, showing that blood flow control cannot be described by a linear control system and that the mechanisms responsible for vasodilation are dependent on work rate.

Animals↗

A new two-breath technique for extracting the cerebrovascular response to arterial carbon dioxide.

Cerebrovascular autoregulation is evaluated from spontaneous fluctuations in mean flow velocity (MFV) by transcranial Doppler ultrasound of the middle cerebral artery (MCA) with respect to changes in arterial blood pressure (BP(MCA)), but the effects of spontaneous fluctuations in arterial Pco(2) on MFV have been largely ignored. Autoregressive moving average analysis (ARMA), a closed-loop system identification technique, was applied to data from nine healthy subjects during spontaneous breathing, during inspiration of 10% CO(2) for two breaths once per minute for 4 min, and during sustained breathing of 7% CO(2). Cerebrovascular resistance index (CVRi) was calculated (CVRi = BP(MCA)/MFV). Reliable estimates of gain for BP(MCA) --> MFV were obtained for spontaneous breathing and the two-breath method. In contrast, reliable gain estimates for Pco(2) --> MFV or Pco(2) --> CVRi were achieved only under the two-breath method. Pco(2) --> MFV gain was smaller with the two-breath method than during sustained 7% CO(2) (P < 0.05). BP(MCA) was elevated by 7% CO(2) but not by the two-breath method. The closed-loop model provides insight into interactions between BP(MCA) and Pco(2) on cerebrovascular control, but reliable solutions for Pco(2) effects with ARMA analysis require perturbation by the two-breath method.

Adult↗

Heart rate variability after prolonged spaceflights.

Astronauts returning from spaceflight often experience post-flight orthostatic intolerance. This study was designed to determine whether cosmonauts with post-flight syncope could be distinguished from those with no post-flight syncope. The autonomic function was determined in a group of ten subjects, with no previous history of syncope, during a stand test before and after a long-term spaceflight (90 to 198 days). Heart rate (HR) and systolic blood pressure (SBP) were measured beat-by-beat, pre- and post-flight and the spontaneous baroreflex sensitivity and HR variability were studied. Individuals were categorized according to their ability to remain standing for 5 min the day after landing. Three of the ten cosmonauts failed to finish the standing test performed the day after landing (nonfinishers). The spontaneous baroreflex slope was reduced in both groups after the spaceflight. The non-finisher group had a lower SBP (P < 0.05) at rest in pre-flight tests than the group that completed the test (finisher group). The non-finisher group also had higher indicators of parasympathetic activity when supine, both pre- and post-flight, but this difference disappeared with standing. At the end of the stand test, SBP and HR were lower in non-finisher cosmonauts than the finishers, while HR did not increase compared to early measurements in the stand test of the finisher group. These results suggest an impairment in autonomic control of HR, which might contribute to the fainting response.

Adult↗

Cerebral hemodynamics and resistance exercise.

PURPOSE: Repetitive resistance exercise with large muscle mass causes rapid fluctuations in mean arterial blood pressure (MAP). We sought to determine the effect of these fluctuations on the cerebrovasculature response determined by mean flow velocity (Vmean) of the middle cerebral artery. METHODS: Nine subjects performed 10-repetition maximum leg press exercise. MAP was estimated by finger photoplethysmography, Vmean by Doppler ultrasound, and end-tidal CO2 (PETCO2) by mass spectrometry. RESULTS: Vmean fluctuated with MAP with each repetition however averaged over the 10 repetitions, Vmean was unchanged from resting baseline values (66.9 +/- 10.8 vs 67.7 +/- 12.3 cm.s-1, baseline vs exercise, P > 0.05) despite an increased MAP (89.5 +/- 8.4 vs 105.0 +/- 4.9 Torr, P < 0.05). PETCO2 also remained unchanged from rest to exercise (37.7 +/- 2.8 vs 36.6 +/- 2.7 Torr, P > 0.05). Vmean decreased below resting levels for the first 5 s of recovery (59.8 +/- 9.1 cm.s-1, P < 0.05) as MAP returned rapidly to slightly below baseline (83.3 +/- 6.1, P > 0.05). MAP/Vmean, an index of cerebrovascular resistance, was elevated during exercise and returned to baseline after exercise. An increase in Vmean at 30 s post exercise (78.4 +/- 10.6 cm.s-1, P < 0.05) corresponded with elevated PETCO2 (43.0 +/- 4.8 Torr, P > 0.05). CONCLUSION: The results suggest that fluctuations in MAP with individual muscle contractions during resistance exercise appear to be too rapid to be countered by cerebrovascular autoregulation. However, the progressive increase in MAP over a number of contractions was effectively countered to maintain Vmean near baseline values before a decrease in Vmean immediately after exercise.

Adult↗

Dynamic modulation of cerebrovascular resistance as an index of autoregulation under tilt and controlled PET(CO(2)).

Transfer function analysis of the arterial blood pressure (BP)-mean flow velocity (MFV) relationship describes an aspect of cerebrovascular autoregulation. We hypothesized that the transfer function relating BP to cerebrovascular resistance (CVRi) would be sensitive to low-frequency changes in autoregulation induced by head-up tilt (HUT) and altered arterial PCO(2). Nine subjects were studied in supine and HUT positions with end-tidal PCO(2) (PET(CO(2))) kept constant at normal levels: +5 and -5 mmHg. The BP-MFV relationship had low coherence at low frequencies, and there were significant effects of HUT on gain only at high frequencies and of PCO(2) on phase only at low frequencies. BP --> CVRi had coherence >0.5 from very low to low frequencies. There was a significant reduction of gain with increased PCO(2) in the very low and low frequencies and with HUT at the low frequency. Phase was affected by PCO(2) in the very low frequencies. Transfer function analysis of BP --> CVRi provides direct evidence of altered cerebrovascular autoregulation under HUT and higher levels of PCO(2).

Adult↗