Effects of blood-volume distribution on the characteristics of the carotid baroreflex in humans at rest and during exercise

Seven supine subjects were studied at rest and during mild to moderate dynamic leg exercise with and without unloading of the cardiopulmonary baroreceptors accomplished by exposing the lower portion of the body to a subatmospheric pressure of 20 mmHg (Lower Body Negative Pressure, LBNP). The function of the cardiac branch of the carotid baroreflex was studied over its full operational range by measuring R-R intervals during application of pulse synchronous graded pressures (40 to – 65 mmHg) in a neck-chamber device. Raising the carotid transmural pressure (systolic arterial pressure minus neck-chamber pressure) induced increasing R-R intervals in all conditions. In conformity with previous results from our laboratories it was found that the maximal rate of change in relative R-R intervals and the corresponding transmural pressure were higher during exercise than at rest, indicating that exercise increased the carotid baroreflex sensitivity and shifted its optimal buffering range to higher arterial pressures. LBNP did not affect the characteristics of the reflex at rest nor during exercise. It is concluded that reduced central venous pressure with consequent selective cardiopulmonary receptor disengagement exerts no influence on the carotid baroreflex control of heart rate (HR), as tested over the entire arterial pressure-effector response relation, either at rest or during mild-moderate exercise.     

Characteristics of the carotid baroreflex in man during normal and flow-restricted exercise.

Eight subjects were studied in the supine position at rest, during normal dynamic leg exercise (control exercise) and with blood-flow restriction in the working legs (flow-restricted exercise). Graded muscle blood-flow restriction was accomplished by applying a supra-atmospheric pressure of 50 mmHg to the working legs. During incremental-load exercise, flow restriction reduced exercise performance and peak heart rate by 36% and 13%, respectively. The function of the cardiac branch of the carotid baroreflex was studied over its full operational range, at rest and during constant-load control and flow-restricted exercise, by measuring R-R intervals during application of pulse-synchronous graded pressures (40 to -65 mmHg) in a neck-chamber device. Heart rate and arterial pressure were higher during flow-restricted than control exercise, indicating that the flow restriction activated the muscle chemoreflex. Raising the carotid transmural pressure (systolic arterial pressure minus neck-chamber pressure) was accompanied by increasing R-R intervals in all conditions. The set point (point of baseline carotid transmural pressure and R-R interval) coincided with the midportion of the pressure-response curve at rest and with the threshold point of the curve during exercise. The maximal rate of change in relative R-R intervals and the corresponding carotid transmural pressure range were higher during control exercise than at rest and highest during flow-restricted exercise, indicating that exercise and especially flow-restricted exercise increased carotid baroflex sensitivity, and shifted the carotid baroreflex optimal buffering range to higher pressures. The results suggest that the carotid baroflex attenuates exercise heart rate increases mediated by the muscle chemoreflex and/or by central command.     

The carotid baroreflex is reset following prolonged exercise in humans

Aim: Alterations in the carotid baroreflex (CBR) control of arterial pressure may explain the reduction in arterial pressure and left ventricular (LV) function after prolonged exercise. We examined the CBR control of heart rate (HR) and mean arterial pressure (MAP), in addition to changes in LV function, pre- to post-exercise. Methods: Seven males (age, mean ± SEM; 29 ± 4 years) completed 4 h of ergometer rowing at a workload of 10–15% below the lactate threshold. The CBR control of HR and MAP was assessed via the rapid neck-suction/pressure protocol. LV systolic function was measured by echocardiography, where ejection fraction (EF), the ratio of systolic blood pressure to end systolic volume (SBP/ESV) and stroke volume (SV) were estimated. Results: Following exercise MAP was reduced (12 ± 3%) and HR was elevated (35 ± 5%; P < 0.05). Furthermore, CBR control of MAP was relocated to the left on the stimulus–response curve (P < 0.05) demonstrating that the CBR operated around a lower arterial pressure. Concomitantly, LV systolic function was reduced, indicated by a decrease in EF (22 ± 2%), SBP/ESV (32 ± 14%) and SV (25 ± 5%, P < 0.05). The reduced EF and SBP/ESV were associated with the decreased MAP operating point (r² = 0.71 and r² = 0.47, respectively, P < 0.05). Conclusion: The CBR is reset after prolonged exercise to a lower prevailing arterial pressure. This resetting of the CBR may contribute to the reduction arterial pressure and LV function after exercise.     

Autonomic nervous control of the heart rate during isometric exercise in normal man

The relative contribution of the efferent components of the autonomic nervous system to the regulation of tachycardia induced by isometric exercise was assessed in 23 normal males. The isometric exercise (handgrip) was performed at the maximum intensity tolerated by the individual over a period of 10 s (maximal voluntary contraction — MVC) and at levels equivalent to 75, 50 and 25% of MVC for 20, 40 and 10 s, respectively. The study was performed both under control conditions and after pharmacological blockade with atropine (12 individuals) or propranolol (11 individuals). Under control conditions, the heart rate (HR) responses to isometric effort were dependent on the intensity and duration of the exercise, showing a tendency towards progressive elevation with the maintenance of muscular contraction at the levels studied. The tachycardia evoked by this effort was of considerable magnitude and of rapid onset, especially at the more intense levels of activity. Parasympathetic blockade markedly decreased tachycardia, which manifested itself during the first 10 s of exercise at all levels of intensity, whereas sympathetic blockade markedly modified the HR response after 10 s of effort at the 75 and 50% MVC levels. A slight depression of the tachycardiac response could be observed already after 10 s of maximum effort after propranolol. The present results suggest that the autonomic regulation of these responses is based on a biphasic mechanism, with the initial phase depending on the rapid withdrawal of the parasympathetic influence, followed by a marked sympathetic contribution to the induction of tachycardia after 10 s of isometric contraction or even a little before at maximum exertion.     

Respiratory and circulatory responses to sustained positive-pressure breathing and exercise in man

To investigate the effects of sustained positive-pressure breathing (PPB) on the adaptation of respiratory and circulatory functions to exercise, 8 healthy volunteers were exposed to PPB of air at 15 and 30 cm H₂O in the supine position at rest and while performing leg exercise at 50% of individual maximal working capacity. PPB was both subjectively and objectively better tolerated when combined with exercise than it was at rest. PPB at 30 cm H_aO resulted in marked hyperventilation with alkalosis in the resting condition, but did not significantly affect respiratory minute volume, blood gases or acid-base balance during exercise. Cardiac output and left ventricular work were reduced by about one fifth and one third, respectively, both at rest and during exercise. In contrast to the case at normal airway pressure, exercise-induced increase in cardiac output was accompanied by an increment in stroke volume during PPB. Although mean arterial pressure (relative to atmospheric) was elevated by PPB at rest and during exercise, the driving pressure in systemic circuits (arterial minus central venous pressure) was reduced in both conditions. It is concluded that dynamic exercise counteracts deleterious effects of PPB by normalizing respiratory function and by improving cardiac filling by activation of the leg muscle and the abdominal pumps.     

Autonomic activity and baroreflex sensitivity in patients submitted to carotid stenting

Arterial baroreflex and cardiac autonomic control play important roles in hemodynamic instability after carotid artery stenting (CAS). Spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and blood pressure variability (BPV) are established tools for the assessment of arterial baroreflex and cardiac autonomic activity. Aim of the study was to evaluate cardiac autonomic activity (by means of HRV, BPV and BRS) after CAS and to explore the impact of internal carotid artery stenosis on BRS changes after CAS. 37 patients (68±10.45 years) with internal carotid stenosis underwent CAS. HRV, BPV and BRS were measured in all subjects before and at 1 and 72h after CAS. ANOVA was performed to compare BRS, HRV and BPV parameters before and after CAS. Spearman analysis was performed to determine a possible correlation between carotid stenosis degree (or carotid plaque diameter) and BRS changes (ΔBRS). LF/HF (index of sympatho-vagal balance) decreased during postoperative period, in comparison with baseline (2.32±1.70 vs 1.65±1.40, p<0.05). There was a significant negative correlation between carotid stenosis degree and ΔBRS (r=-0.35, p=0.03) and between carotid plaques thickness and ΔBRS (r=-0.36, p=0.02). CAS procedure may cause an alteration of carotid wall mechanical properties, increasing baroreflex sensitivity. BRS does not increase in all the patients, because arterial wall damage and nerve destruction determined by atherosclerotic plaque may reduce ΔBRS.     

Baroreflex control of sinus node during dynamic exercise in humans: effect of muscle mechanoreflex

Aim: This study evaluated the influence of muscle mechanical afferent stimulation on the integrated arterial baroreflex control of the sinus node during dynamic exercise. Methods: Systolic blood pressure (SBP) and pulse interval (PI) were measured continuously and non‐invasively in 15 subjects at rest and during passive cycling. The arterial baroreflex was evaluated with the cross‐correlation method (xBRS) for the computation of time‐domain baroreflex sensitivity on spontaneous blood pressure and PI variability. xBRS computes the greatest positive correlation between beat‐to‐beat SBP and PI, and when significant at P = 0.01, slope and delay are recorded as one xBRS value. Heart rate variability (HRV) was evaluated in the frequency domain. Results: Compared with rest, passive exercise resulted in a parallel increase in heart rate (67 ± 3.2 vs. 70 ± 3.6 beats min^?1; P < 0.05) and mean arterial pressure (87 ± 2 vs. 95 ± 2 mmHg; P < 0.05), and a significant decrease in xBRS (13.1 ± 1.8 vs. 10.5 ± 1.7 ms mmHg^?1; P < 0.01) with an apparent rightward shift in the regression line relating SBP to PI. Also low frequency power of HRV increased while high frequency power decreased (56.7 ± 3.5 vs. 62.7 ± 4.8 and 43.2 ± 3.4 vs. 36.9 ± 4.9 normalized units respectively; P < 0.05). Conclusion: These data suggest that the stimulation of mechanosensitive stretch receptors is capable of modifying the integrated baroreflex control of sinus node function by decreasing the cardiac vagal outflow during exercise.     

Role of central command in carotid baroreflex resetting in humans during static exercise

The purpose of the experiments was to examine the role of central command in the exercise-induced resetting of the carotid baroreflex. Eight subjects performed 30 % maximal voluntary contraction (MVC) static knee extension and flexion with manipulation of central command (CC) by patellar tendon vibration (PTV). The same subjects also performed static knee extension and flexion exercise without PTV at a force development that elicited the same ratings of perceived exertion (RPE) as those observed during exercise with PTV in order to assess involvement of the exercise pressor reflex. Carotid baroreflex (CBR) function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid changes in neck pressure and suction during steady state static exercise. Knee extension exercise with PTV (decreased CC activation) reset the CBR-HR and CBR-MAP to a lower operating pressure ( P < 0.05) and knee flexion exercise with PTV (increased CC activation) reset the CBR-HR and CBR-MAP to a higher operating pressure ( P < 0.05). Comparison between knee extension and flexion exercise at the same RPE with and without PTV found no difference in the resetting of the CBR-HR function curves ( P > 0.05) suggesting the response was determined primarily by CC activation. However, the CBR-MAP function curves were reset to operating pressures determined by both exercise pressor reflex (EPR) and central command activation. Thus the physiological response to exercise requires CC activation to reset the carotid-cardiac reflex but requires either CC or EPR to reset the carotid-vasomotor reflex.     

The use of isometric exercise as a means of evaluating the parasympathetic contribution to the tachycardia induced by dynamic exercise in normal man

Fourteen normal subjects were submitted to isometric exercise (IE), dynamic exercise (DE) and a combination of the two (IE+DE). The main purpose of the present study was to use IE as a means of evaluating the mechanism of the heart rate (HR) increase induced by DE. To this end, the magnitude of the IE (handgrip) was standardized so as to cause an elevation of HR almost exclusively by vagal withdrawal: IE was performed using a dynamometer straingauge system with a linear response at 75% of maximum voluntary contraction (MVC) for 10s, repeated at 1 min intervals. The change in HR evoked by IE under control conditions was compared with that evoked during DE, and during the corresponding recovery period. DE was performed by the legs, with the subject in the seated position for 4 min, at workloads of 55 and 105 watts, separated by a rest period. In the combined protocol, IE was performed at the beginning of DE, as well as at 1, 2 and 3 min during DE, and at 0, 1, 2, 3 and 5 min during recovery period. The following results were obtained: (1) IE associated with DE always induced smaller increase in heart rate than IE alone, and this effect was more marked at 105 than at 55W; this finding suggested a workload-dependent vagal withdrawal at the very beginning of DE that was sustained until the end of effort. (2) During DE, each IE induced a similar increase in HR, even at workload of 105 W, when the HR increased gradually in response to DE itself; these results suggest that, this gradual tachycardia (from the 1st to the 4th min of DE) was not vagus dependent. (3) The standardized IE used here permitted functional evaluation of the dynamics of vagal withdrawal without resorting to pharmacological blockade of the autonomic nervous system.Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (79/1798-3) e Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq-300528-85/CL)     

Pain sensitivity in offspring of hypertensives at rest and during baroreflex stimulation

Healthy males with a parental history of hypertension (PH+) showed reduced pain sensitivity to a constrictive thigh-cuff pressure stimulus as compared to individuals without a parental history of hypertension. The protocol included eight trials in which a thigh-cuff was inflated until the subject reported the stimulus to be painful. The PH+ group exhibited significantly lower pain sensitivity as indicated by (1) higher levels of constrictive pressure when pain was first reported and (2) lower subjective pain ratings at maximum constrictive pressure. To assess the role of baroreflex stimulation on pain sensitivity in these groups, four trials were administered concurrently with external carotid pressure stimulation. There were no significant differences in pain sensitivity in each group as a function of baroreflex stimulation. The results suggest that the hypoalgesia observed in hypertensives may predate the development of sustained elevations in blood pressure.     

Increases in central blood volume modulate carotid baroreflex resetting during dynamic exercise in humans

We sought to determine if resetting of the carotid-vasomotor baroreflex function curve during exercise is modulated by changes in central blood volume (CBV). CBV was increased during exercise by altering: (1) subject posture (supine versus upright) and (2) pedal frequency (80 versus 60 revolutions min⁻¹ (r.p.m.)); while oxygen uptake (     ) was kept constant. Eight male subjects performed three exercise trials: upright cycling at 60 r.p.m. (control); supine cycling at 60 r.p.m. (SupEX) and upright cycling at 80 r.p.m. to enhance the muscle pump (80EX). During each condition, carotid baroreflex (CBR) function was determined using the rapid neck pressure (NP) and neck suction (NS) protocol. Although mean arterial pressure (MAP) was significantly elevated from rest (88 ± 2 mmHg) during all exercise conditions ( P < 0.001), the increase in MAP was lower during SupEX (94 ± 2 mmHg) and 80EX (95 ± 2 mmHg) compared with control (105 ± 2 mmHg, P < 0.05). Importantly, the blood pressure responses to NP and NS were maintained around these changed operating points of MAP. However, in comparison to control, the carotid-vasomotor baroreflex function curve was relocated downward and leftward when CBV was increased during SupEX and 80EX. These alterations in CBR resetting occurred without any differences in     or heart rate between the exercise conditions. Thus, increasing CBV and loading the cardiopulmonary baroreflex reduces the magnitude of exercise-induced increases in MAP and CBR resetting. These findings suggest that changes in cardiopulmonary baroreceptor load influence carotid baroreflex resetting during dynamic exercise.     

Hormonal,immune, and oxidative stress responses to blood flow-restricted exercise

Introduction

Heavy-load free-flow resistance exercise (HL-FFRE) is a widely used training modality. Recently, low-load blood-flow restricted resistance exercise (LL-BFRRE) has gained attention in both athletic and clinical settings as an alternative when conventional HL-FFRE is contraindicated or not tolerated. LL-BFRRE has been shown to result in physiological adaptations in muscle and connective tissue that are comparable to those induced by HL-FFRE. The underlying mechanisms remain unclear; however, evidence suggests that LL-BFRRE involves elevated metabolic stress compared to conventional free-flow resistance exercise (FFRE).

Aim

The aim was to evaluate the initial (<10 min post-exercise), intermediate (10–20 min), and late (>30 min) hormonal, immune, and oxidative stress responses observed following acute sessions of LL-BFRRE compared to FFRE in healthy adults.

Methods

A systematic literature search of randomized and non-randomized studies was conducted in PubMed, Embase, Cochrane Central, CINAHL, and SPORTDiscus. The Cochrane Risk of Bias (RoB2, ROBINS-1) and TESTEX were used to evaluate risk of bias and study quality. Data extractions were based on mean change within groups.

Results

A total of 12525 hits were identified, of which 29 articles were included. LL-BFRRE demonstrated greater acute increases in growth hormone responses when compared to overall FFRE at intermediate (SMD 2.04; 95% CI 0.87, 3.22) and late (SMD 2.64; 95% CI 1.13, 4.16) post-exercise phases. LL-BFRRE also demonstrated greater increase in testosterone responses compared to late LL-FFRE.

Conclusion

These results indicate that LL-BFRRE can induce increased or similar hormone and immune responses compared to LL-FFRE and HL-FFRE along with attenuated oxidative stress responses compared to HL-FFRE.     

Stroke volume decreases during mild dynamic and static exercise in supine humans

Aim: The contributions of cardiac output (CO) and total peripheral resistance to changes in arterial blood pressure are debated and differ between dynamic and static exercise. We studied the role stroke volume (SV) has in mild supine exercise. Methods: We investigated 10 healthy, supine volunteers by continuous measurement of heart rate (HR), mean arterial blood pressure, SV (ultrasound Doppler) and femoral beat volume (ultrasound Doppler) during both dynamic mild leg exercise and static forearm exercise. This made it possible to study CO, femoral flow (FF) and both total and femoral peripheral resistance beat‐by‐beat. Results: During a countdown period immediately prior to exercise, HR and mean arterial pressure increased, while SV decreased. During mild supine exercise, SV decreased by 5–8%, and most of this was explained by increased mean arterial pressure. Dynamic leg exercise doubled femoral beat volume, while static hand grip decreased femoral beat volume by 18%. FF is tightly regulated according to metabolic demand during both dynamic leg exercise and static forearm exercise. Conclusion: Our three major findings are, firstly, that SV decreases during both dynamic and static mild supine exercise due to an increase in mean arterial pressure. Secondly, femoral beat volume decreases during static hand grip, but FF is unchanged due to the increase in HR. Finally, anticipatory responses to exercise are apparent prior to both dynamic and static exercise. SV changes contribute to CO changes and should be included in studies of central haemodynamics during exercise.     

Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans

We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with β₁-adrenergic blockade (metoprolol, 0.15 ± 0.003 mg kg⁻¹) or parasympathetic blockade (glycopyrrolate, 13.6 ± 1.5 μg kg⁻¹). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to −80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise ( P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain ( G _max) of the CBR-HR function curve (−0.58 ± 0.10 to −0.06 ± 0.01 beats min⁻¹ mmHg⁻¹, P < 0.05), but had no effect on the G _max of the CBR-MAP function curve. During isometric exercise the CBR-HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate ( P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in G _max. Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise.     

Arterial blood pressure and carotid baroreflex function during arm and combined arm and leg exercise in humans

AIM: During arm cranking (A) blood pressure is higher than during combined arm and leg exercise (A + L), while the carotid baroreflex (CBR) is suggested to reset to control a higher blood pressure in direct relation to work intensity and the engaged muscle mass. METHOD: This study evaluated the function of the CBR by using neck pressure and neck suction during upright A, L and A + L in 12 subjects and, in order to evaluate a potential influence of the central blood volume on the CBR, also during supine A in five subjects. Exercise intensities for A and L were planned to elicit a heart rate response of c. 100 and 120 beats min(-1), respectively, in the upright position and both workloads were maintained during A + L and supine A. RESULTS: The CBR operating point, corresponding to the pre-stimulus blood pressure, was 88 +/- 6 mmHg (mean +/- SE) at rest. During upright A, L and A + L and supine A it increased to 109 +/- 9, 95 +/- 7, 103 +/- 7 and 104 +/- 4 mmHg, respectively, and it was thus higher during upright A than during A + L and supine A (P < 0.05). In addition, the CBR threshold and saturation pressures, corresponding to the minimum and maximum carotid sinus pressure, respectively, were higher during upright A than during supine A, A + L, L and at rest (P < 0.05) with no significant change in the maximal reflex gain. CONCLUSION: These findings demonstrate that during combined arm and leg and exercise in the upright position the CBR resets to a lower blood pressure than during arm cranking likely because the central blood volume is enhanced by the muscle pump of the legs.