A closed-loop approach to the study of the baroreflex dynamics during posture changes at rest and at exercise in humans

We hypothesized that during rapid up-tilting at rest, due to vagal withdrawal, arterial baroreflex sensitivity (BRS) may decrease promptly and precede the operating point (OP) resetting, whereas different kinetics are expected during exercise steady state, due to lower vagal activity than at rest. To test this, eleven subjects were rapidly (< 2s) tilted from supine (S) to upright (U) and vice versa every 3 minutes, at rest and during steady state 50W pedaling. Mean arterial pressure (MAP) was measured by finger cuff (Portapres) and R-to-R interval (RRi) by electrocardiography. BRS was computed with the sequence method both during steady and unsteady states. At rest, BRS was 35.1ms∙mmHg-1 (SD17.1) in S and 16.7ms∙mmHg-1 (SD6.4) in U (p<0.01), RRi was 901ms (SD118) in S and 749ms (SD98) in U (p<0.01), and MAP was 76mmHg (SD11) in S and 83mmHg (SD8) in U (p<0.01). During up-tilt, BRS decreased promptly [first BRS sequence was 19.7ms∙mmHg-1 (SD5.0)] and was followed by an OP resetting (MAP increase without changes in RRi). At exercise, BRS and OP did not differ between supine and upright positions [respectively, BRS was 7.7ms∙mmHg-1 (SD3.0) and 7.7ms∙mmHg-1 (SD3.5), MAP was 85mmHg (SD13) and 88mmHg (SD10), and RRi was 622ms (SD61) and 600ms (SD70)]. The results support the tested hypothesis. The prompt BRS decrease during up-tilt at rest may be ascribed to a vagal withdrawal, similarly to what occurs at exercise onset. The OP resetting may be due to a slower control mechanism, possibly an increase in sympathetic activity.

GABAA receptor activation modulates the muscle sympathetic nerve activity responses at the onset of static exercise in humans

Exercise is a well-known sympathoexcitatory stimulus. However, muscle sympathetic nerve activity (MSNA) can decrease during the onset of muscle contraction. Yet, the underlying mechanisms and neurotransmitters involved in the sympathetic responses at the onset of exercise remain unknown. Herein, we tested the hypothesis that GABAA receptors may contribute to the MSNA responses at the onset of static handgrip in humans. Thirteen young, healthy individuals (4 females) performed 30 s of ischemic static handgrip at 30% of maximum volitional contraction before and following oral administration of either placebo or diazepam (10 mg), a benzodiazepine that enhances GABAA activity. MSNA (microneurography), beat-to-beat blood pressure (finger photopletysmography), heart rate (electrocardiogram) and stroke volume (ModelFlow) were continuously measured. Cardiac output (CO = stroke volume x heart rate) and total vascular conductance (TVC = CO / mean blood pressure) were subsequently calculated. At rest, MSNA was reduced while hemodynamic variables were unchanged after diazepam administration. Before diazepam, static handgrip elicited a significant decrease in MSNA burst frequency (∆-7±2 bursts/min, P<0.01 vs. baseline) and MSNA burst incidence (∆-16±2 bursts/100 heart beats, P<0.01 vs. baseline); however, these responses were attenuated following diazepam administration (∆-1±2 bursts/min and ∆-7±2 bursts/100 heart beats, respectively; P<0.01 vs. before diazepam). Diazepam did not affect the increases in heart rate, blood pressure, CO and TVC at the exercise onset. Importantly, the placebo had no effect on any variable at rest or exercise onset. These findings suggest that GABAA receptor activation modulates the MSNA responses at the onset of static exercise in young, healthy humans.

Vagal blockade suppresses the phase I heart rate response but not the phase I cardiac output response at exercise onset in humans

Purpose We tested the vagal withdrawal concept for heart rate (HR) and cardiac output (CO) kinetics upon moderate exercise onset, by analysing the effects of vagal blockade on cardiovascular kinetics in humans. We hypothesized that, under atropine, the φ1 amplitude (A1) for HR would reduce to nil, whereas the A1 for CO would still be positive, due to the sudden increase in stroke volume (SV) at exercise onset. Methods On nine young non-smoking men, during 0–80 W exercise transients of 5-min duration on the cycle ergometer, preceded by 5-min rest, we continuously recorded HR, CO, SV and oxygen uptake ($$ \dot{V} $$ V ˙ O2) upright and supine, in control condition and after full vagal blockade with atropine. Kinetics were analysed with the double exponential model, wherein we computed the amplitudes (A) and time constants (τ) of phase 1 (φ1) and phase 2 (φ2). Results In atropine versus control, A1 for HR was strongly reduced and fell to 0 bpm in seven out of nine subjects for HR was practically suppressed by atropine in them. The A1 for CO was lower in atropine, but not reduced to nil. Thus, SV only determined A1 for CO in atropine. A2 did not differ between control and atropine. No effect on τ1 and τ2 was found. These patterns were independent of posture. Conclusion The results are fully compatible with the tested hypothesis. They provide the first direct demonstration that vagal blockade, while suppressing HR φ1, did not affect φ1 of CO.

Central command-related increases in blood velocity of anterior cerebral artery and prefrontal oxygenation at the onset of voluntary tapping

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increases prior to and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so, mean blood velocity of the ACA (ACABV) should increase with "very light motor effort", concomitantly with the pre-exercise and initial increase in prefrontal Oxy-Hb. This study aimed to examine the responses in ACABV and vascular conductance index (ACAVCI) of the ACA as well as prefrontal Oxy-Hb during arbitrary or cued finger-tapping in 12 subjects, an activity with a Borg scale perceived exertion rating of 7 (median). With arbitrary start, ACABV increased at tapping onset (14 ± 9%) via an elevation in ACAVCI. Likewise, prefrontal Oxy-Hb increased at the onset of tapping with a time course resembling that of ACABV. A positive cross-correlation between the initial changes in ACABV and prefrontal Oxy-Hb was found significant in 67% of subjects, having a time lag of 2 s, while a positive linear regression between them was significant in 75% of subjects. When tapping was forced to start by cue, the initial increases in ACABV, ACAVCI, and prefrontal Oxy-Hb were delayed and blunted as compared to an arbitrary start. Thus active vasodilatation of the ACA vascular bed occurs at tapping onset, as long as tapping is arbitrarily started, and contributes to immediate increases in blood flow and prefrontal oxygenation.

Sex differences in the physiological responses to exercise-induced dehydration: Consequences and mechanisms?

Physiological strain during exercise is increased by mild dehydration (~1-3% body mass loss). This response may be sex-dependent but there are no direct comparative data in this regard. This review aimed to develop a framework for future research by exploring the potential impact of sex on thermoregulatory and cardiac strain associated with exercise-induced dehydration. Sex-based comparisons were achieved by comparing trends from studies that implemented similar experimental protocols but recruited males and females separately. This revealed a higher core temperature (Tc) in response to exercise-induced dehydration in both sexes, however it seemingly occurred at a lower percent body mass loss in females. Although less clear, similar trends existed for cardiac strain. The average female may have a lower body water volume per body mass compared to males, and therefore the same % body mass loss between the sexes may represent a larger portion of total body water in females potentially posing a greater physiological strain. Additionally, the rate which Tc increases at exercise onset might be faster in females and induce a greater thermoregulatory challenge earlier into exercise. The Tc response at exercise onset is associated with lower sweating rates in females, which is commonly attributed to sex-differences in metabolic heat production. However, a reduced sweat gland sensitivity to stimuli, lower fluid output per sweat gland, and sex hormones promoting fluid retention in females may also contribute. In conclusion, the limited evidence suggests sex-based differences exist in thermoregulatory and cardiac strain associated with exercise-induced dehydration, and this warrants future investigations.

Cardiorespiratory responses to exercise related to post-stroke fatigue severity

Physical deconditioning after stroke may induce post-stroke fatigue. However, research on this association is limited. Our primary objective was to investigate the associations of post-stroke fatigue severity with oxygen uptake ($$\dot{\mathrm{V}}$$ V ˙ O2) at peak exercise and the time constant of $$\dot{\mathrm{V}}$$ V ˙ O2 kinetics (τ$$\dot{\mathrm{V}}$$ V ˙ O2) at exercise onset. The secondary objective was to examine the associations between fatigue and cardiorespiratory variables potentially affecting $$\dot{\mathrm{V}}$$ V ˙ O2 during exercise. Twenty-three inpatients from a subacute rehabilitation ward were enrolled in this study. The median (interquartile range) Fatigue Severity Scale (FSS) score, as a measure of fatigue, was 32 (range 27–42) points. The FSS score was not associated with $$\dot{\mathrm{V}}$$ V ˙ O2 at peak exercise during a symptom-limited graded exercise test (rho = − 0.264; p = 0.224), whereas it was significantly associated with τ$$\dot{\mathrm{V}}$$ V ˙ O2 during a submaximal constant-load exercise test (rho = 0.530; p = 0.009). A higher FSS score also significantly correlated with a longer time constant of cardiac output (CO) kinetics (rho = 0.476; p = 0.022). Our findings suggest that severe post-stroke fatigue is associated with delayed increases in $$\dot{\mathrm{V}}$$ V ˙ O2 and CO at the onset of exercise. Our findings can contribute to the development of an appropriate rehabilitation programme for individuals with post-stroke fatigue.

Carbohydrate Requirements for Prolonged, Fasted Exercise with and without Basal Rate Reductions in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion (CSII)

<b>Objective:</b> Exercising while fasted in type 1 diabetes facilitates weight loss, however the best strategy to maintain glucose stability remains unclear. <p><b>Research Design and Methods:</b> Fifteen adults on CSII completed three sessions of fasted walking (120min at 45%VO_2peak) in a randomized crossover design: 50% basal rate reduction set 90min pre-exercise (-90_min50%_BRR); usual basal rate with carbohydrate intake (0.3g/kg/hr; CHO-only); and combined 50%basal rate reduction set at exercise onset with carbohydrate (0.3g/kg/hr; Combo). </p> <p><b>Results:</b> Combo had a smaller change in glucose (5±47mg/dL) vs CHO-only (-49±61mg/dL, <i>P</i>=0.03) or -90_min50%_BRR (-34±45mg/dL). -90_min50%_BRR produced higher b-hydroxybutyrate levels (0.4±0.3 vs 0.1±0.1mmol/L) and greater fat oxidation (0.51±0.2 vs 0.39±0.1g/min) than CHO-only (both <i>P</i><0.05).</p> <b>Conclusions:</b> All strategies examined produced stable glycemia for fasted exercise, but a 50%basal rate reduction set 90 min pre-exercise eliminates carbohydrate needs and enhances fat oxidation better than carbohydrate feeding with or without a basal rate reduction set at exercise onset.

Carbohydrate Requirements for Prolonged, Fasted Exercise with and without Basal Rate Reductions in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion (CSII)

<b>Objective:</b> Exercising while fasted in type 1 diabetes facilitates weight loss, however the best strategy to maintain glucose stability remains unclear. <p><b>Research Design and Methods:</b> Fifteen adults on CSII completed three sessions of fasted walking (120min at 45%VO_2peak) in a randomized crossover design: 50% basal rate reduction set 90min pre-exercise (-90_min50%_BRR); usual basal rate with carbohydrate intake (0.3g/kg/hr; CHO-only); and combined 50%basal rate reduction set at exercise onset with carbohydrate (0.3g/kg/hr; Combo). </p> <p><b>Results:</b> Combo had a smaller change in glucose (5±47mg/dL) vs CHO-only (-49±61mg/dL, <i>P</i>=0.03) or -90_min50%_BRR (-34±45mg/dL). -90_min50%_BRR produced higher b-hydroxybutyrate levels (0.4±0.3 vs 0.1±0.1mmol/L) and greater fat oxidation (0.51±0.2 vs 0.39±0.1g/min) than CHO-only (both <i>P</i><0.05).</p> <b>Conclusions:</b> All strategies examined produced stable glycemia for fasted exercise, but a 50%basal rate reduction set 90 min pre-exercise eliminates carbohydrate needs and enhances fat oxidation better than carbohydrate feeding with or without a basal rate reduction set at exercise onset.