Min Of Post-exercise Circulatory Occlusion Research Articles

Cardiovascular reflex contributions to sympathetic inhibition during low intensity dynamic leg exercise in healthy middle-age.

Aging augments resting muscle sympathetic nerve activity (MSNA) and sympatho-inhibition during mild dynamic 1-leg exercise. To elucidate which reflexes elicit exercise-induced inhibition, we recruited 19 (9 men) healthy volunteers (mean age 56 ± 9 SD years), assessed their peak oxygen uptake (VO2peak ), and, on another day, measured heart rate (HR), blood pressure (BP) and MSNA (microneurography) at rest and during 1-leg cycling (2 min each at 0 load and 30%-40% VO2peak ), 3 times: (1) seated +2 min of postexercise circulatory occlusion (PECO) (elicit muscle metaboreflex); (2) supine (stimulate cardiopulmonary baroreflexes);and (3) seated, breathing 32% oxygen (suppress peripheral chemoreceptor reflex). While seated, MSNA decreased similarly during mild and moderate exercise (p < 0.001) with no increase during PECO (p = 0.44). Supine posture lowered resting MSNA (main effect p = 0.01) BP and HR. MSNA fell further (p = 0.04) along with diastolic BP and HR during mild, not moderate, supine cycling. Hyperoxia attenuated resting (main effect p = 0.01), but not exercise MSNA. In healthy middle-age, the cardiopulmonary baroreflex and arterial chemoreflex modulate resting MSNA, but contrary to previous observations in young subjects, without counter-regulatory offset by the sympatho-excitatory metaboreflex, resulting in an augmented sympatho-inhibitory response to mild dynamic leg exercise.

Hemodynamic responses to handgrip and metaboreflex activation are exaggerated in individuals with metabolic syndrome independent of resting blood pressure, waist circumference, and fasting blood glucose.

Introduction: Prior studies report conflicting evidence regarding exercise pressor and metaboreflex responses in individuals with metabolic syndrome (MetS). Purpose: To test the hypotheses that 1) exercise pressor and metaboreflex responses are exaggerated in MetS and 2) these differences may be explained by elevated resting blood pressure. Methods: Blood pressure and heart rate (HR) were evaluated in 26 participants (13 MetS) during 2min of handgrip exercise followed by 3min of post-exercise circulatory occlusion (PECO). Systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP), along with HR and a cumulative blood pressure index (BPI), were compared between groups using independent samples t-tests, and analyses of covariance were used to adjust for differences in resting blood pressure, fasting blood glucose (FBG), and waist circumference (WC). Results: ΔSBP (∼78% and ∼54%), ΔMAP (∼67% and ∼55%), and BPI (∼16% and ∼20%) responses were significantly exaggerated in individuals with MetS during handgrip and PECO, respectively (all p ≤ 0.04). ΔDBP, ΔMAP, and BPI responses during handgrip remained significantly different between groups after independently covarying for resting blood pressure (p < 0.01), and after simultaneously covarying for resting blood pressure, FBG, and WC (p ≤ 0.03). Likewise, peak SBP, DBP, MAP, and BPI responses during PECO remained significantly different between groups after adjusting for resting blood pressure (p ≤ 0.03), with peak SBP, MAP, and BPI response remaining different between groups after adjusting for all three covariates simultaneously (p ≤ 0.04). Conclusion: These data suggest that exercise pressor and metaboreflex responses are significantly exaggerated in MetS independent of differences in resting blood pressure, FBG, or WC.

Blood Pressure Responses to Postexercise Circulatory Occlusion Are Attenuated After Exercise-Induced Muscle Weakness.

Exercise blood pressure (BP) responses are thought to be determined by relative exercise intensity (percent maximal voluntary contraction (MVC) strength). However, cross-sectional studies report that during a static contraction, higher absolute force is associated with greater BP responses to relative intensity exercise and subsequent muscle metaboreflex activation with postexercise circulatory occlusion (PECO). We hypothesized that a bout of unaccustomed eccentric exercise would reduce knee extensor MVC and subsequently attenuate BP responses to PECO. Continuous BP, heart rate, muscle oxygenation, and knee extensor electromyography were recorded in 21 young healthy individuals (female, n = 10) during 2 min of 20% MVC static knee extension exercise and 2 min of PECO, performed before and 24 h after 300 maximal knee extensor eccentric contractions to cause exercise-induced muscle weakness. As a control, 14 participants repeated the eccentric exercise 4 wks later to test whether BP responses were altered when exercise-induced muscle weakness was attenuated via the protective effects of the repeated bout effect. Eccentric exercise reduced MVC in all participants (144 ± 43 vs 110 ± 34 N·m, P < 0.0001). BP responses to matched relative intensity static exercise (lower absolute force) were unchanged after eccentric exercise ( P > 0.99) but were attenuated during PECO (systolic BP: 18 ± 10 vs 12 ± 9 mm Hg, P = 0.02). Exercise-induced muscle weakness modulated the deoxygenated hemoglobin response to static exercise (64% ± 22% vs 46% ± 22%, P = 0.04). When repeated after 4 wks, exercise-induced weakness after eccentric exercise was attenuated (-21.6% ± 14.3% vs -9.3 ± 9.7, P = 0.0002) and BP responses to PECO were not different from control values (all, P > 0.96). BP responses to muscle metaboreflex activation, but not exercise, are attenuated by exercise-induced muscle weakness, indicating a contribution of absolute exercise intensity on muscle metaboreflex activation.

Acute changes in forearm vascular compliance during transient sympatho-excitation.

The study of vascular regulation often omits important information about the elastic properties of arteries under conditions of pulsatile flow. The purpose of this study was to examine the relationship between muscle sympathetic nerve activity (MSNA), vascular bed compliance, and peripheral blood flow responses in humans. We hypothesized that increases in MSNA would correlate with reductions in vascular compliance, and that changes in compliance would correspond with changes in peripheral blood flow during sympatho‐excitation. MSNA (microneurography), blood pressure (Finopres), and brachial artery blood flow (Doppler ultrasound), were monitored in six healthy males at baseline and during the last 15 s of voluntary end‐inspiratory, expiratory apneas and 5 min of static handgrip exercise (SHG; 20% maximum voluntary contraction) and 3 min of post‐exercise circulatory occlusion (SHG + PECO; measured in the non‐exercising arm). A lumped Windkessel model was employed to examine vascular bed compliance. During apnea, indices of MSNA were inversely related with vascular compliance, and reductions in compliance correlated with decreased brachial blood flow rate. During SHG, despite increased MSNA, compliance also increased, but was unrelated to increases in blood flow. Neither during SHG nor PECO did indices of MSNA correlate with forearm vascular compliance nor did vascular compliance correlate with brachial flow. However, during PECO, a linear combination of blood pressure and total MSNA was correlated with vascular compliance. These data indicate the elastic components of the forearm vasculature are regulated by adrenergic and myogenic mechanisms during sympatho‐excitation, but in a reflex‐dependent manner.

Cardiorespiratory responses to muscle metaboreflex activation in fibrosing interstitial lung disease.

New Findings What is the central question of this study? We determined whether sensory feedback from metabolically sensitive skeletal muscle afferents (metaboreflex) causes a greater ventilatory response and higher dyspnoea ratings in fibrosing interstitial lung disease (FILD). What is the main finding and its importance? Ventilatory responses and dyspnoea ratings during handgrip exercise and metaboreflex isolation were not different in FILD and control groups. Blood pressure and heart rate responses to handgrip were attenuated in FILD but not different to controls during metaboreflex isolation. These findings suggest that the muscle metaboreflex contribution to the respiratory response to exercise is not altered in FILD. Exercise limitation and dyspnoea are hallmarks of fibrosing interstitial lung disease (FILD); however, the physiological mechanisms are poorly understood. In other respiratory diseases, there is evidence that an augmented muscle metaboreflex may be implicated. We hypothesized that metaboreflex activation in FILD would result in elevated ventilation and dyspnoea ratings compared to healthy controls, due to augmented muscle metaboreflex. Sixteen FILD patients (three women, 69±14 years; mean±SD) and 16 age‐matched controls (four women, 67±7 years) were recruited. In a randomized cross‐over design, participants completed two min of rhythmic handgrip followed by either (i) two min of post‐exercise circulatory occlusion (PECO trial) to isolate muscle metaboreflex activation, or (ii) rested for four min (Control trial). Minute ventilation (V˙E; pneumotachometer), dyspnoea ratings (0–10 Borg scale), mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR; electrocardiogram) were measured. V˙E was higher in the FILD group at baseline and exercise increased V˙E similarly in both groups. V˙E remained elevated during PECO, but there was no between‐group difference in the magnitude of this response (ΔV˙E FILD 4.2 ± 2.5 L·min–1 vs. controls 3.6 ± 2.4 L·min–1, P = 0.596). At the end of PECO, dyspnoea ratings in FILD were similar to controls (1.0 ± 1.3 units vs. 0.5 ± 1.1 units). Exercise increased MAP and HR (P < 0.05) in both groups; however, responses were lower in FILD. Collectively, these findings suggest that there is not an augmented effect of the muscle metaboreflex on breathing and dyspnoea in FILD, but haemodynamic responses to handgrip are reduced relative to controls.

Impaired sympathetic neural recruitment during exercise pressor reflex activation in women with post-traumatic stress disorder.

Muscle sympathetic nerve activity (MSNA) increases during isometric exercise via increased firing of low-threshold action potentials (AP), recruitment of larger, higher-threshold APs, and synaptic delay modifications. Recent work found that women with post-traumatic stress disorder (PTSD) demonstrate exaggerated early-onset MSNA responses to exercise; however, it is unclear how PTSD affects AP recruitment patterns during fatiguing exercise. We hypothesized that women with PTSD (n = 11, 43[11] [SD] years) would exhibit exaggerated sympathetic neural recruitment compared to women without PTSD (controls; n = 13, 40[8] years). MSNA and AP discharge patterns (via microneurography and a continuous wavelet transform) were measured during 1 min of baseline, isometric handgrip exercise (IHG) to fatigue, 2 min of post-exercise circulatory occlusion (PECO), and 3 min of recovery. Women with PTSD were unable to increase AP content per burst compared to controls throughout IHG and PECO (main effect of group: P = 0.026). Furthermore, relative to controls, women with PTSD recruited fewer AP clusters per burst during the first (controls: ∆1.3[1.2] vs. PTSD: ∆-0.2[0.8]; P = 0.016) and second minute (controls: ∆1.2[1.1] vs. PTSD: ∆-0.1[0.8]; P = 0.022) of PECO, and fewer subpopulations of larger, previously silent axons during the first (controls: ∆5[4] vs. PTSD: ∆1[2]; P = 0.020) and second minute (controls: ∆4[2] vs. PTSD: ∆1[2]; P = 0.021) of PECO. Conversely, PTSD did not modify the AP cluster size-latency relationship during baseline, the end of IHG, or PECO (all P = 0.658-0.745). Collectively, these data indicate that women with PTSD demonstrate inherent impairments in the fundamental neural coding patterns elicited by the sympathetic nervous system during IHG and exercise pressor reflex activation.

Sex Differences in Muscle Metaboreflex Activation after Static Handgrip Exercise.

Larger blood pressure (BP) responses to relative-intensity static exercise in men versus women are thought to involve altered muscle metaboreflex activation, but whether this is because of an intrinsic sex difference in metabolite production or differences in muscle strength and absolute load is unknown. Continuous BP and heart rate were recorded in 200 healthy young men and women (women: n = 109) during 2 min of static handgrip exercise at 30% of maximal voluntary contraction (MVC), followed by 2 min of postexercise circulatory occlusion (PECO). Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (n = 39; women, n = 21), permitting calculation of signal-averaged resting sympathetic transduction (MSNA-diastolic BP). Sex differences were examined with and without statistical adjustment for MVC. Multivariate regression analyses were performed to identify predictors of BP responses. Men had larger systolic BP responses (interactions, P < 0.0001) to static handgrip exercise (24 ± 10 vs 17 ± 9 mm Hg [mean ± SD], P < 0.0001) and PECO (20 ± 11 vs 16 ± 9 mm Hg, P < 0.0001). Adjustment for MVC abolished these sex differences in BP (interactions, P > 0.7). In the subset with MSNA, neither burst frequency or incidence responses to static handgrip exercise or PECO differed between men and women (interactions, P > 0.2). Resting sympathetic transduction was also similar (P = 0.8). Multiple linear regression analysis showed that MVC or the change in MSNA, were predictors of BP responses to static handgrip, but only MVC was associated with BP responses during PECO. Sex differences in absolute contraction load contribute to differences in BP responses during muscle metaboreflex isolation using PECO. These data do not support an intrinsic effect of sex as being responsible for exercise BP differences between men and women.

Muscle Metaboreflex Control of Sympathetic Activity Is Preserved after Acute Intermittent Hypercapnic Hypoxia.

In normotensive patients with obstructive sleep apnea (OSA), the muscle sympathetic nerve activity (MSNA) response to exercise is increased while metaboreflex control of MSNA is decreased. We tested the hypotheses that acute intermittent hypercapnic hypoxia (IHH) in males free from OSA and associated comorbidities would augment the MSNA response to exercise but attenuate the change in MSNA during metaboreflex activation. Thirteen healthy males (age = 24 ± 4 yr) were exposed to 40 min of IHH. Before and after IHH, the pressor response to exercise was studied during 2 min of isometric handgrip exercise (at 30% maximal voluntary contraction), whereas the metaboreflex was studied during 4 min of postexercise circulatory occlusion (PECO). Mean arterial pressure (MAP), heart rate (HR), and fibular MSNA were recorded continuously. MSNA was quantified as burst frequency (BF) and total activity (TA). Mixed effects linear models were used to compare the exercise pressor and metaboreflex before and after IHH. As expected, IHH led to significant increases in MSNA BF, TA, and MAP at baseline and throughout exercise and PECO. However, during handgrip exercise, the change from baseline in MAP, HR, MSNA BF, and TA was similar before and after IHH (All P > 0.31). During PECO, the change from baseline in MSNA BF and TA was similar after IHH, whereas the change from baseline in MAP (Δ14 mm Hg, 95% CI = 7-19, vs Δ16 mm Hg, 95% CI = 10-21; P < 0.01) was modestly increased. After acute IHH, MSNA response to handgrip exercise and metaboreflex activation were preserved in healthy young males despite overall increases in resting MSNA and MAP. Chronic IHH and comorbidities often associated with OSA may be required to modulate the exercise pressor reflex and metaboreflex.

The sympathetic muscle metaboreflex is not different in the third trimester in normotensive pregnant women.

Isometric handgrip (IHG) is used to assess sympathetic nervous system responses to exercise and may be useful at predicting hypertension in both pregnant and nonpregnant populations. We previously observed altered sympathetic nervous system control of blood pressure in late pregnancy. Therefore, we measured muscle sympathetic nerve activity (MSNA) and blood pressure during muscle metaboreflex activation (IHG) in normotensive pregnant women in the third trimester compared with in healthy nonpregnant women. Further, 19 pregnant (32 ± 3 wk gestation) and 14 nonpregnant women were matched for age, non/prepregnant body mass index (BMI), and parity. MSNA (microneurography), heart rate (ECG), and arterial blood pressure (Finometer) were continuously recorded during 10 min of rest, and then during 2 min of IHG at 30% of maximal voluntary contraction, and 2 min of postexercise circulatory occlusion (PECO). Baseline sympathetic nerve activity (SNA) was elevated in pregnant (41 ± 11 bursts/min) compared with nonpregnant women (27 ± 9 bursts/min; P = 0.005); however, the sympathetic baroreflex gain and neurovascular transduction were not different between groups (P = 0.62 and P = 0.32, respectively). During IHG and PECO, there were no significant differences in the pressor responses (ΔMAP) between groups, (P = 0.25, main effect of group) nor was the sympathetic response different between groups (interaction effect: P = 0.16, 0.25, and 0.27 for burst frequency, burst incidence, and total SNA, respectively). These data suggest that pregnant women who have maintained sympathetic baroreflex and neurovascular transduction also have similar sympathetic and pressor responses during exercise.NEW & NOTEWORTHY We compared sympathetic nervous system activation by muscle metaboreflex between pregnant women in the third trimester and nonpregnant women. We show that the sympathetic nerve activity and associated pressor responses to isometric handgrip and post-exercise circulatory occlusion are not different between third-trimester pregnant and nonpregnant women. These data suggest that unlike other reflexes (e.g., cold pressor test or head-up tilt), metaboreflex control is maintained in pregnant women.

Oral contraceptives and menstrual cycle influence autonomic reflex function

Progesterone and its analogues are known to influence ventilation. Therefore, the purpose of this study was to investigate the role of endogenous and pharmaceutical female sex hormones in ventilatory control during the activation of the metaboreflex, mechanoreflex, and CO2 chemoreflex. Women aged 18–30 taking (n = 14) or not taking (n = 12) oral contraceptives (OC and NOC, respectively) were tested in the low hormone (LH) and high hormone (HH) conditions corresponding to the early follicular and mid‐luteal phases (NOC) or placebo and high‐dose pills (OC). Women underwent three randomized trials: (a) 3 min of passive leg movement (PLM), (b) 2 min of 40% maximal voluntary handgrip exercise followed by 2 min of post‐exercise circulatory occlusion (PECO), and (c) 5 min of breathing 5% CO2. We primarily measured hemodynamics and ventilation. During PLM, the OC group had a smaller pressor response (p = .012). During PECO, the OC group similarly exhibited a smaller pressor response (p = .043) and also exhibited a greater ventilatory response (p = .024). Lastly, in response to breathing 5% CO2, women in the HH phase had a greater ventilatory response (p = .022). We found that OC use attenuates the pressor response to both the metaboreflex and mechanoreflex while increasing the ventilatory response to metaboreflex activation. We also found evidence of an enhanced CO2 chemoreflex in the HH phase. We hypothesize that OC effects are from the chronic upregulation of pulmonary and vascular β‐adrenergic receptors. We further suggest that the increased cyclic progesterone in the HH phase enhances the chemoreflex.

Sex differences in blood pressure regulation during ischemic isometric exercise: the role of the β-adrenergic receptors.

We sought to investigate whether the β-adrenergic receptors play a pivotal role in sex-related differences in arterial blood pressure (BP) regulation during isometric exercise. Sixteen volunteers (8 women) performed 2 min of ischemic isometric handgrip exercise (IHE) and 2 min of postexercise circulatory occlusion (PECO). Heart rate (HR) and beat-to-beat arterial BP were continuously measured. Beat-to-beat estimates of stroke volume (ModelFlow) were obtained and matched with HR to calculate cardiac output (Q̇) and total peripheral resistance (TPR). Two trials were randomly conducted between placebo and nonselective β-adrenergic blockade (40 mg propranolol). Under the placebo condition, the magnitude of the BP response in IHE was lower in women compared with men. During PECO, the BP remained elevated and the sex differences persisted. The β-blockade attenuated the BP response during IHE in men (∆57 ± 4 vs. ∆45 ± 7 mmHg, P = 0.025) due to a reduction in Q̇ (∆3.7 ± 0.5 vs. ∆1.8 ± 0.2 L/min, P = 0.012) while TPR was not affected. In women, however, the BP response during IHE was unchanged (∆27 ± 3 vs. ∆28 ± 3 mmHg, P = 0.889), despite attenuated Q̇ (∆2.7 ± 0.4 vs. ∆1.3 ± 0.2 L/min, P = 0.012). These responses were mediated by a robust increase in TPR under β-blockade (∆-0.2 ± 0.4 vs. ∆2.2 ± 0.7 mmHg·L-1·min, P = 0.012). These findings demonstrate that the sex differences in arterial BP regulation during ischemic IHE are mediated by β-adrenergic receptors.NEW & NOTEWORTHY We found that the blood pressure response during isometric exercise in women is mediated by increases in cardiac output, whereas in men it is mediated by increases in both cardiac output and total peripheral resistance. In addition, women showed a robust increase in total peripheral resistance under β-blockade during isometric exercise and muscle metaboreflex activation. These findings demonstrate that sex differences in blood pressure regulation during isometric exercise are mediated by β-adrenergic receptors.

The Ventilatory Response to Muscle Metaboreflex Activation During Concurrent Hypercapnia is Attenuated by Local Muscle Training

Increased ventilation during post‐exercise circulatory occlusion (PECO) with concurrent hypercapnia suggests a synergistic interaction between muscle metaboreflex activation and chemoreflex stimulation. The exercise pressor reflex (EPR) response to contraction of a human calf muscle and subsequent PECO can be attenuated by training, indicating a decreased activation of muscle metaboreceptive afferents driving the EPR. We hypothesised that 6 weeks of one legged calf raise training would attenuate metaboreceptor activity, the EPR and if these afferents provide a drive to breathe, the ventilatory response seen during PECO when combined with mild hypercapnia. In the contralateral limb there would be no effect on muscle afferent input to the cardiovascular or respiratory control systems so no change in EPR or breathing would be expected during PECO.Eleven male subjects aged 19.5 ± 0.8 years (mean±SD) gave informed consent to participate in the study, approved by the local ethics committee. A standardized test of the cardiovascular and respiratory responses to isometric contraction of the calf muscle at 50% of maximum voluntary force (MVC) for 2 min was followed by 3 min of PECO. In random order left and right legs were tested separately under two conditions, 1) breathing room air 2) hypercapnia, 5% CO2 above end tidal level. A dynamic end tidal forcing system controlled the inspired gas composition and monitored ventilation. Heart rate (HR) and blood pressure (MAP) were measured by ECG and Portapres respectively. Right leg training consisted of 120 calf raises to maximum height in 4 sets of 30, one heel raise and lower per second, one minute rest between sets. Whenever 4 sets could be achieved loading of 10%, then increments of 5% body mass was added. After 6 weeks of training the initial tests were repeated.MVC did not change after training in either leg. During exercise of the trained leg during hypercapnia, average MAP rise from baseline was reduced from 18.1± 1.4, to 15.6±1.4 mmHg (mean±SEM), p&lt;0.05 after, training. Ventilation change from the hypercapnic baseline was also reduced from 17.5± 2.8 to 12.1±2.6 l.min−1, p&lt;0.05 after training.Table 1 shows the data from each leg in the PECO phase of the trials, performed before and after the training. In the room air and hypercapnia trials, the EPR was significantly reduced from control values in the trained leg. The increase in ventilation from baseline was reduced, by ~45%, in the trained limb during the hypercapnia trial. There were no alterations in the cardiovascular or ventilatory responses to PECO, during hypercapnia or room air breathing trials in the untrained limb, ruling out any central or peripheral adaptation in this leg, induced by the training period. In the trained leg the MAP data shows clear evidence of a decrease in the EPR after training, indicating reduced muscle metaboreflex activation during PECO. This is despite generating the same force‐time integral during the exercise period as before training. We conclude that in the trained limb the marked decrease in ventilation during PECO in the hypercapnia condition must be due to a decreased drive to breathe arising from metabosensitive muscle afferents.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ischemic preconditioning does not alter muscle sympathetic responses to static handgrip and metaboreflex activation in young healthy men.

Ischemic preconditioning (IPC) has been hypothesized to elicit ergogenic effects by reducing feedback from metabolically sensitive group III/IV muscle afferents during exercise. If so, reflex efferent neural outflow should be attenuated. We investigated the effects of IPC on muscle sympathetic nerve activity (MSNA) during static handgrip (SHG) and used post‐exercise circulatory occlusion (PECO) to isolate for the muscle metaboreflex. Thirty‐seven healthy men (age: 24 ± 5 years [mean ± SD]) were randomized to receive sham (n = 16) or IPC (n = 21) interventions. Blood pressure, heart rate, and MSNA (microneurography; sham n = 11 and IPC n = 18) were collected at rest and during 2 min of SHG (30% maximal voluntary contraction) and 3 min of PECO before (PRE) and after (POST) sham or IPC treatment (3 × 5 min 20 mmHg or 200 mmHg unilateral upper arm cuff inflation). Resting mean arterial pressure was higher following sham (79 ± 7 vs. 83 ± 6 mmHg, P < 0.01) but not IPC (81 ± 6 vs. 82 ± 6 mmHg, P > 0.05), while resting MSNA burst frequency was unchanged (P > 0.05) with sham (18 ± 7 vs. 19 ± 9 bursts/min) or IPC (17 ± 7 vs. 19 ± 7 bursts/min). Mean arterial pressure, heart rate, stroke volume, cardiac output, and total vascular conductance responses during SHG and PECO were comparable PRE and POST following sham and IPC (All P > 0.05). Similarly, MSNA burst frequency, burst incidence, and total MSNA responses during SHG and PECO were comparable PRE and POST with sham and IPC (All P > 0.05). These findings demonstrate that IPC does not reduce hemodynamic responses or central sympathetic outflow directed toward the skeletal muscle during activation of the muscle metaboreflex using static exercise or subsequent PECO.

The effect of slow-loaded breathing training on the blood pressure response to handgrip exercise in patients with isolated systolic hypertension.

Isolated systolic hypertension (ISH) is the most common form of hypertension in older people. It is characterized by increased resting systolic blood pressure (sBP) and increased sBP in response to exercise. It has previously been shown that slow breathing training reduces resting sBP, and the objective of the present study was to determine whether it also reduced the blood pressure response to static handgrip exercise. ISH patients aged between 60 and 74 years were randomly divided into a control group (10 subjects, 4 of which were male) that breathed normally and a trained group (10 subjects, 4 of which were male) that trained daily for 8 weeks by slow breathing against an inspiratory resistance of 18 cmH2O. Before and immediately after training, subjects underwent a 2-min handgrip test (30% max) followed by 2 min of post-exercise circulatory occlusion (PECO) to assess metaboreflex activity. Training reduced sBP by 10.6 mm Hg (95% confidence interval (CI), -16 to -5 mm Hg, P=0.004), but changes were not observed in the control group. The peak exercise sBP was reduced by 23 mm Hg (95% CI, -16 to -31 mm Hg, P<0.001), while the increase in the sBP above resting was reduced by 12.6 mm Hg (95% CI, -6.9 to -18.2 mm Hg, P=0.002). The sBP during PECO was reduced by 8.9 mm Hg (95% CI, -4 to -14 mm Hg, P=0.008), which is indicative of reduced metaboreflex activity; no such change was observed in the control group. The results demonstrate that conventional treatment of older patients with ISH may be improved in two ways by slow breathing training: resting sBP may be reduced by 10 mm Hg, more than can be achieved by conventional pharmacological therapies, while the response to static exercise may be reduced by approximately twice this value.

Sex difference in the influence of central blood volume mobilization on the exercise pressor response.

To determine the sex difference in the impact of central venous pressure (CVP) on the pressor response induced by ischemic handgrip exercise. Twelve young healthy individuals (six males, 25 ± 3 years) performed ischemic handgrip exercise during mild levels of lower body negative pressure (LBNP, -5 mmHg) and during a 10° head-down tilt (HDT) to lower and increase CVP, respectively. The protocol consisted of 3 min of baseline ischemia, followed by 2 min of isometric handgrip exercise at 35 % of maximal voluntary contraction force, and 2 min of post-exercise circulatory occlusion. Mean arterial pressure (MAP) was assessed continuously by finger plethysmography and CVP was estimated from the venous pressure of the non-exercising dependent arm. Baseline CVP was greater during HDT than LBNP (8.4 ± 1.8 vs. 6.5 ± 1.8 mmHg, p < 0.01). MAP was greater during LBNP than HDT throughout the protocol (p = 0.05). During ischemic handgrip exercise, CVP increased in males but not in females (Group × protocol interaction: p = 0.01). A group × condition interaction was also observed for MAP, with males showing a greater MAP during LBNP than HDT (110 ± 2 vs. 103 ± 2 mmHg, p < 0.01). Baseline CVP inversely affected the pressor response to handgrip exercise in all individuals, with a greater MAP response observed during LBNP than HDT. Increase in CVP in males may be due to a greater splanchnic vasoconstrictor response to ischemic handgrip exercise. Therefore, combined baseline CVP and changes in CVP likely contributed to the greater MAP response observed during LBNP in males.

Mechanisms of ventilatory control: who is really in charge?

Mechanisms of ventilatory control: who is really in charge?

Activation of the carotid chemoreflex secondary to muscle metaboreflex stimulation in men

Recent work has shown that the carotid chemoreceptor (CC) contributes to sympathetic control of cardiovascular function during exercise, despite no evidence of increased circulating CC stimuli, suggesting enhanced CC activity/sensitivity. As interactions between metaboreceptors and chemoreceptors have been previously observed, the purpose of this study was to isolate the metaboreflex while acutely stimulating or inhibiting the CC to determine whether the metaboreflex increased CC activity/sensitivity. Fourteen young healthy men (height: 177.0 ± 2.1 cm, weight: 85.8 ± 5.5 kg, age: 24.6 ± 1.1 yr) performed three trials of 40% maximal voluntary contraction handgrip for 2 min, followed by 3 min of postexercise circulatory occlusion (PECO) to stimulate the metaboreflex. In random order, subjects either breathed room air, hypoxia (target SPo2 = 85%), or hyperoxia (FiO2 = 1.0) during the PECO to modulate the chemoreflex. After these trials, a resting hypoxia trial was conducted without handgrip or PECO. Ventilation (Ve), heart rate (HR), blood pressure, and muscle sympathetic nervous activity (MSNA) data were continuously obtained. Relative to normoxic PECO, inhibition of the CC during hyperoxic PECO resulted in lower MSNA (P = 0.038) and HR (P = 0.021). Relative to normoxic PECO, stimulation of the CC during hypoxic PECO resulted in higher HR (P < 0.001) and Ve (P < 0.001). The ventilatory and MSNA responses to hypoxic PECO were not greater than the sum of the responses to hypoxia and PECO individually, indicating that the CC are not sensitized during metaboreflex activation. These results demonstrate that stimulation of the metaboreflex activates, but does not sensitize the CC, and help explain the enhanced CC activity with exercise.

A respiratory response to the activation of the muscle metaboreflex during concurrent hypercapnia in man

In this study, we aimed to assess the ventilatory and cardiovascular responses to the combined activation of the muscle metaboreflex and the ventilatory chemoreflex, achieved by postexercise circulatory occlusion (PECO) and euoxic hypercapnia (end-tidal partial pressure of CO2 7 mmHg above normal), respectively. Eleven healthy subjects (4 women and 7 men; 29 +/- 4.4 years old; mean +/- S.D.) undertook the following four trials, in random order: 2 min of isometric handgrip exercise followed by 2 min of PECO with hypercapnia; 2 min of isometric handgrip exercise followed by 2 min of PECO while breathing room air; 4 min of rest with hypercapnia; and 4 min of rest while breathing room air. Ventilation was significantly increased during exercise in both the hypercapnic (+3.17 +/- 0.82 l min(-1)) and the room air breathing trials (+2.90 +/- 0.26 l min(-1); all P < 0.05). During PECO, ventilation returned to pre-exercise levels when breathing room air (+0.52 +/- 0.37 l min(-1); P > 0.05), but it remained elevated during hypercapnia (+3.77 +/- 0.23 l min(-1); P < 0.05). The results indicate that the muscle metaboreflex stimulates ventilation with concurrent chemoreflex activation. These findings have implications for disease states where effort intolerance and breathlessness are linked.

Central command and metaboreflex cardiovascular responses to sustained handgrip during microgravity

Four subjects were studied before and during a 16-day space flight. The test included 2min of rest, 2min of sustained handgrip (SHG), and 2min of post-exercise circulatory occlusion (PECO). Heart rate (HR) and mean arterial pressure (MAP) responses to central command and mechanoreceptor stimulation were determined from the difference between SHG and PECO. Responses to metaboreceptor stimulation were determined from the difference between PECO and rest. Late in-flight (days 12-14) the central command/mechanoreceptor component of the HR response was reduced by 5bpm (P=0.01) from its pre-flight value of 15 (+/-3)bpm (mean (+/-SEM)). At the same time the metaboreflex responses of HR and MAP were unchanged. The attenuated HR response to central command was likely of baroreflex origin. Together with a parallel study of PECO after dynamic leg exercise, our data indicate that central processing of metaboreflex inputs is unchanged in microgravity whereas metaboreflex inputs from weight-bearing muscles are enhanced.

WISE 2005: stroke volume changes contribute to the pressor response during ischemic handgrip exercise in women

The mechanism of the pressor response to small muscle mass (e.g., forearm) exercise and during metaboreflex activation may include elevations in cardiac output (Q) or total peripheral resistance (TPR). Increases in Q must be supported by reductions in visceral venous volume to sustain venous return as heart rate (HR) increases. Therefore, this study tested the hypothesis that increases in Q, supported by reductions in splanchnic volume (portal vein constriction), explain the pressor response during handgrip exercise and metaboreflex activation. Seventeen healthy women performed 2 min of static ischemic handgrip exercise and 2 min of postexercise circulatory occlusion (PECO) while HR, stroke volume and superficial femoral artery flow (Doppler), blood pressure (Finometer), portal vein diameter (ultrasound imaging), and muscle sympathetic nerve activity (MSNA; microneurography) were measured followed by the calculation of Q, TPR, and leg vascular resistance (LVR). Compared with baseline, mean arterial blood pressure (MAP) (P < 0.001) and Q (P < 0.001) both increased in each minute of exercise accompanied by a approximately 5% reduction in portal vein diameter (P < 0.05). MAP remained elevated during PECO, whereas Q decreased below exercise levels. MSNA was elevated above baseline during the second minute of exercise and through the PECO period (P < 0.05). Neither TPR nor LVR was changed from baseline during exercise and PECO. The data indicate that the majority of the blood pressure response to isometric handgrip exercise in women was due to mobilization of central blood volume and elevated stroke volume and Q rather than elevations in TVR or LVR resistance.