Circulatory Occlusion Research Articles

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.

Hemodynamic responses to neuromuscular electrical stimulation and to metaboreflex activation.

Metabolites produced during muscle exercise can sensitize types III and IV fibers, which account for increasing blood pressure (BP) and vascular resistance in non-exercising limbs, as well as for redistributing the blood flow to active muscles; reflex response is called metaboreflex. Neuromuscular electrical stimulation (NMES) induces greater local muscle metabolic demand than voluntary isometric contractions. Metabolic accumulation is essential to activate muscle metaboreflex; thus, the hypothesis of the current study is that one NMES session can induce metaboreflex with different hemodynamic responses in upper and lower limbs. Objective - to investigate whether one acute NMES session could activate metaboreflex by inducing different hemodynamic responses between arms and legs. Twenty (20) healthy subjects (mean age = 47.7±9.4 years, 13 women, mean body mass index = 26 ± 3 kg/m2) participated in this randomized crossover study. All participants were subjected to two NMES interventions, one in the upper limbs (UPL) and the other in the lower limbs (LL). Mean blood pressure (MBP), blood flow (BF) and vascular resistance (VR) were used to selectively evaluate metaboreflex responses at baseline, during NMES interventions, and recovery periods with, and without, postexercise circulatory occlusion (PECO+ and PECO-, respectively) through the area under the curve (AUC) in VR. MBP increased by 13% during UPL interventions and only remained high during PECO+. Changes in MBP were not observed in LL, although BF in the contralateral leg has decreased by 14% during PECO+ protocol. Muscle metaboreflex activation (AUC differences in VR between PECO+ and PECO-) was not different between UPL and LL (P=0.655). Acute NMES session has induced similar metaboreflex activation in both arms and legs, although hemodynamic responses differed between interventions.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Investigating the control of exercise hyperpnoea: A synergy of contributions.

Metaboreflex Activity is Attenuated by Transcutaneous Electrical Nerve Stimulation and Interferential Electrical Stimulation in Healthy Individuals

Background: Transcutaneous electrical nervous stimulation (TENS) and interferential electrical stimulation (IES) attenuates muscle metaboreflex by sympathetic nervous modulation. Objective: We tested the hypothesis that IES may be more effective than TENS to improves blood flow which may be linked to greater of deep tissue. Methods: Eleven health subjects were randomized to TENS (80 Hz, 150μs), IES (4000 Hz, ΔAMF=25 Hz) or sham stimulation group, during 30 minutes. The acute intervention was applied on stellate ganglion region (C7-T4). Results: Were measured metaboreflex activity by calf vascular resistance (CVR) and calf blood flow (CBF) and HRV during three times: rest, exercise (static handgrip) and postexercise circulatory occlusion (PECO+ and PECO-). At the exercise peak, compared with TENS and Sham, the IES group reduced CVR (36 ± 3 vs 43 ± 3; p&lt;0.05) and increased CBF (p&lt;0.01). Also, IES was associated with a greater reduction on the MMA (IES: 9 ± 2, TENS: 14 ± 4, Sham: 26 ± 5 units; p&lt;0.01). Furthermore, the IES group had a higher reduction of LF/HF ratio during PECO- and PECO+ (p&lt;0.05). Conclusion: The IES over the stellate ganglion region seems to have superior efficacy compared with TENS to attenuate metaboreflex activation and vasodilatory responses during exercise in healthy subjects.

Sex differences in the coronary vascular response to combined chemoreflex and metaboreflex stimulation in healthy humans.

What is the central question of this study? Coronary blood flow in healthy humans is controlled by both local metabolic signalling and adrenergic activity: does the integration of these signals during acute hypoxia and adrenergic activation differ between sexes? What are the main findings and its importance? Both males and females exhibit an increase in coronary blood velocity in response to acute hypoxia, a response that is constrained by adrenergic stimulation in males but not females. These findings suggest that coronary blood flow control differs between males and females. Coronary hyperaemia is mediated through multiple signalling pathways, including local metabolic messengers and adrenergic stimulation. This study aimed to determine whether the coronary vascular response to adrenergic stressors is different between sexes in normoxia and hypoxia. Young, healthy participants (n=32; 16F) underwent three randomized trials of isometric handgrip exercise followed by post-exercise circulatory occlusion (PECO) to activate the muscle metaboreflex. End-tidal was controlled at (1) normoxic levels throughout the trial, (2) 50mmHg for the duration of the trial (hypoxia trial), or (3) 50mmHg only during PECO (mixed trial). Mean left anterior descending coronary artery velocity (LADVmean ; transthoracic Doppler echocardiography), heart rate and blood pressure were assessed at baseline and during PECO. In normoxia, there was no change in LADVmean or cardiac workload induced by PECO in males and females. Acute hypoxia increased baseline LADVmean to a greater extent in males compared with females (P<0.05), despite a similar increase in cardiac workload. The change in LADVmean induced by PECO was similar between sexes in normoxia (P=0.31), greater in males during the mixed trial (male: 12.8 (7.7) cm/s vs. female: 8.1 (6.3) cm/s; P=0.02) and reduced in males but not females in acute hypoxia (male: -4.8 (4.5) cm/s vs. female: 0.8 (6.2) cm/s; P=0.006). In summary, sex differences in the coronary vasodilatory response to hypoxia were observed, and metaboreflex activation during hypoxia caused a paradoxical reduction in coronary blood velocity in males but not females.

Heart rate and cardiac autonomic responses to concomitant deep breathing, hand grip exercise, and circulatory occlusion in healthy young adult men and women

BackgroundDeep breathing (DB) and handgrip (HG) exercise -with and without circulatory occlusion (OC) in muscle-, have been shown to have beneficial effects on cardiovascular function; however, the combination of these maneuvers on heart rate (HR) and cardiac sympathovagal balance have not been previously investigated. Therefore, the aim of the present study was to evaluate the effect of simultaneous DB, HG, and OC maneuvers on the sympathovagal balance in healthy women and men subjects.Methods and resultsElectrocardiogram and ventilation were measured in 20 healthy subjects (Women: n = 10; age = 27 ± 4 years; weight = 67.1 ± 8.4 kg; and height = 1.6 ± 0.1 m. Men: n = 10; age = 27 ± 3 years; weight = 77.5 ± 10.1 kg; and height = 1.7 ± 0.1 m) at baseline and during DB, DB + HG, or DB + HG + OC protocols. Heart rate (HR) and respiratory rate were continuously recorded, and spectral analysis of heart rate variability (HRV) were calculated to indirectly estimate cardiac autonomic function. Men and women showed similar HR responses to DB, DB + HG and DB + HG + OC. Men exhibited a significant HR decrease following DB + HG + OC protocol which was accompanied by an improvement in cardiac autonomic control evidenced by spectral changes in HRV towards parasympathetic predominance (HRV High frequency: 83.95 ± 1.45 vs. 81.87 ± 1.50 n.u., DB + HG + OC vs. baseline; p < 0.05). In women, there was a marked decrease in HR after completion of both DB + HG and DB + HG + OC tests which was accompanied by a significant increase in cardiac vagal tone (HRV High frequency: 85.29 ± 1.19 vs. 77.93 ± 0.92 n.u., DB + HG vs. baseline; p < 0.05). No adverse effects or discomfort were reported by men or women during experimental procedures. Independent of sex, combination of DB, HG, and OC was tolerable and resulted in decreases in resting HR and elevations in cardiac parasympathetic tone.ConclusionsThese data indicate that combined DB, HG and OC are effective in altering cardiac sympathovagal balance and reducing resting HR in healthy men and women.

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.

Menstrual phase does not influence ventilatory responses to group III/IV afferent signaling in eumenorrheic young females

Estrogen can reduce sympathetic activity, but its effects on minute ventilation (VE) with group III/IV afferent activation remain unclear. This study examined the influence of estrogen on VE during lower-extremity exercise with group III/IV activation. Females completed two identical visits in follicular and ovulatory menstrual phases. Nine participants (age 25 ± 4 years) performed three minutes of baseline steady-state cycle ergometry and then group III/IV afferents were further activated with proximal thigh cuffs inflated to 20, 60, and 100 mmHg (randomized) for two minutes and five minutes of cycling between each occlusion. Metaboreflex was isolated by post-exercise circulatory occlusion. Ventilation was measured continuously and rating of perceived exertion (RPE) was recorded for each stage. During rest and exercise, VE (p < 0.001) and tidal volume (VT) (p = 0.033) were higher in the follicular than ovulatory phase. Minute ventilation, VT, and respiratory rate (RR) with ergoreflex and metaboreflex activation were similar across phases. With cuff occlusion of 100 mmHg, VE increased from baseline by 26.3 ± 7.0 L/min in the follicular phase (p < 0.001) and by 25.3±7.7 L/min in the ovulatory phase (p < 0.001), with no difference between phases (p> 0.05); RR and VT increased similarly with occlusion, also with no phase differences. In eumenorrheic females, menstrual phase influences ventilation but not ventilatory responses to group III/IV isolation.

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.

Sympathetic activation due to limb venous distension is preserved during muscle metaboreceptor stimulation

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans (venous distension reflex). It is unclear if the inputs from metabolically sensitive skeletal muscle afferents (i.e. muscle metaboreflex) would modify venous distension reflex. We hypothesized that muscle metaboreceptor stimulation might augment the venous distension reflex. BP (Finapres), heart rate (ECG), and MSNA (microneurography) were assessed in 18 young healthy subjects. In trial A, saline (5% forearm volume) was infused into the veins of an arterially occluded arm (non-handgrip trial). In trial B, subjects performed 2 min static handgrip followed by post exercise circulatory occlusion (PECO) of the arm. During PECO, saline was infused into veins of the arm (handgrip trial). In trial A, the infusion increased MSNA and BP as expected (both P < 0.001). In trial B, handgrip significantly raised MSNA, BP and venous lactic acid concentrations. Venous saline infusion during PECO further raised MSNA and BP (both P < 0.001). The changes in MSNA (D8.6 ± 1.5 to D10.6 ± 1.8 bursts/min, P = 0.258) and mean arterial pressure (P = 0.844) evoked by the infusion during PECO were not significantly different from those in the non-handgrip trial. These observations indicate that venous distension reflex responses are preserved during sympathetic activation mediated by the muscle metaboreflex.

Exercise Pressor Reflex is Attenuated during Moderate Whole‐Body Heating in Older Humans

Prior reports show that whole-body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole-body heating (WBH, e.g. increase in internal temperature Tcore ~0.4-0.5 °C) on sympathetic and cardiovascular responses to exercise in older healthy humans remains unclear. We examined muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP) and heart rate (HR) in 14 older (62 ± 7 yrs. mean ± SD) healthy subjects during fatiguing isometric handgrip exercise and post exercise circulatory occlusion (PECO). The protocol was performed under normothermic and moderate WBH conditions during 2 visits. Under the moderate WBH condition (ΔTcore ~0.4 ± 0.1 °C), MAP decreased (90.0 ± 6.6 to 86.4 ± 7.1 mmHg), HR increased (60.8 ± 7.9 to 71.7 ± 9.7 beats/min), while MSNA was unchanged (34.7 ± 9.2 to 37.5 ± 15.4 bursts/min) from the baseline before heating. Hemodynamic variables and MSNA did not change significantly during the time control period in the normothermic trial. Compared with the normothermic trial, the absolute MAP during fatiguing exercise (102.7 ± 8.5 vs. 117.2 ± 11.4 mmHg) and PECO (98.2 ± 8.9 vs. 113.9 ± 12.5 mmHg) were lower during the WBH trial. Moreover, MSNA (Δ8.4 ± 6.5 vs. Δ14.0 ± 7.2 bursts/min) and MAP (Δ16.5 ± 7.5 vs. Δ23.2 ± 8.2 mmHg) responses (i.e. changes) to fatiguing exercise were also less than those seen during the normothermic trial. These data suggest that moderate WBH attenuates reflex exercise pressor responses in older healthy humans. Further studies are needed to examine if WBH can attenuate exercise pressor responses in patients with cardiovascular diseases.

Moderate whole body heating attenuates the exercise pressor reflex responses in older humans.

Prior reports show that whole body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole body heating (WBH; e.g., increase in internal temperature Tcore of ∼0.4°C-0.5°C) or limb heating on sympathetic and cardiovascular responses to exercise in older healthy humans remain unclear. We examined the muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and heart rate (HR) in 14 older (62 ± 2 yr) healthy subjects during fatiguing isometric handgrip exercise and postexercise circulatory occlusion (PECO). The protocol was performed under normothermic, moderate WBH, and local limb (i.e., forearm) heating conditions during three visits. During the mild WBH stage (increase in Tcore of <0.3°C), HR increased, whereas BP and MSNA decreased from baseline. Under the moderate WBH condition (increase in Tcore of ∼0.4°C), BP decreased, HR increased, and MSNA was unchanged from baseline. Compared with the normothermic trial, the absolute MAP during fatiguing exercise and PECO was lower during the WBH trial. Moreover, MSNA and MAP responses (i.e., changes) to fatiguing exercise were also less than those seen during the normothermic trial. Limb heating induced a similar increase in forearm muscle temperature to that seen in the WBH trial (∼0.7°C-1.5°C). Limb heating did not alter resting MAP, HR, or MSNA. The MSNA and hemodynamic responses to exercise in the limb heating trial were not different from those in the normothermic trial. These data suggest that moderate WBH attenuates MSNA and BP responses to exercise in older healthy humans.

Disturbed Blood Flow Acutely Increases Endothelial Microparticles and Decreases Flow Mediated Dilation in Patients With Heart Failure With Reduced Ejection Fraction.

IntroductionDisturbed blood flow, characterized by high retrograde and oscillatory shear rate (SR), is associated with a proatherogenic phenotype. The impact of disturbed blood flow in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown. We tested the hypothesis that acute elevation to retrograde and oscillatory SR provoked by local circulatory occlusion would increase endothelial microparticles (EMPs) and decrease brachial artery flow-mediated dilation (FMD) in patients with HFrEF.MethodsEighteen patients with HFrEF aged 55 ± 2 years, with left ventricular ejection fraction (LVEF) 26 ± 1%, and 14 control subjects aged 49 ± 2 years with LVEF 65 ± 1 randomly underwent experimental and control sessions. Brachial artery FMD (Doppler) was evaluated before and after 30 min of disturbed forearm blood flow provoked by pneumatic cuff (Hokanson) inflation to 75 mm Hg. Venous blood samples were collected at rest, after 15 and 30 min of disturbed blood flow to assess circulating EMP levels (CD42b−/CD31+; flow cytometry).ResultsAt rest, FMD was lower in patients with HFrEF compared with control subjects (P < 0.001), but blood flow patterns and EMPs had no differences (P > 0.05). The cuff inflation provoked a greater retrograde SR both groups (P < 0.0001). EMPs responses to disturbed blood flow significantly increased in patients with HFrEF (P = 0.03). No changes in EMPs were found in control subjects (P > 0.05). Disturbed blood flow decreased FMD both groups. No changes occurred in control condition.ConclusionCollectively, our findings suggest that disturbed blood flow acutely decreases FMD and increases EMP levels in patients with HFrEF, which may indicate that this set of patients are vulnerable to blood flow disturbances.

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.

Cardiac autonomic recovery following traditional and augmented remote ischemic preconditioning.

While the possible ergogenic benefits of remote ischemic preconditioning (RIPC) make it an attractive training modality, the mechanisms of action remain unclear. Alterations in neural tone have been demonstrated in conjunction with circulatory occlusion, yet investigation of the autonomic nervous system following RIPC treatment has received little attention. We sought to characterize alterations in autonomic balance to both RIPC and augmented RIPC (RIPCaug) performed while cycling, using acute and sustained autonomic indices. Thirteen participants (8M:5F) recorded baseline waking heart rate variability (HRV) for 5days prior to treatment. Participants then completed control exercise (CON), RIPC, and RIPCaug interventions in a randomized cross-over design. Cardiovascular measurements were recorded immediately before and after each intervention at rest, and during an orthostatic challenge. Waking HRV was repeated the morning after each intervention. RIPC resulted in acutely reduced resting heart rates (HR) (∆-4 ± 6bpm, P = 0.02) and suppressed HR 30s following the orthostatic challenge compared to CON (64 ± 10 vs 74 ± 9bpm, P = 0.003). RIPCaug yielded elevated HRs compared to CON and RIPC prior to (P = 0.003) and during the orthostatic challenge (P = 0.002). RIPCaug reduced LnSDNN (Baseline 4.39 ± 0.27; CON 4.44 ± 0.39; RIPC 4.41 ± 0.34; RIPCaug 4.22 ± 0.29, P = 0.02) and LnHfa power (Baseline 7.82 ± 0.54; CON 7.73 ± 1.11; RIPC 7.89 ± 0.78; RIPCaug 7.23 ± 0.87, P = 0.04) the morning after treatment compared to all other conditions. Our data suggest that RIPC may influence HR acutely, possibly through a reduction in cardiac sympathetic activity, and that RIPCaug reduces HRV through cardiac vagal withdrawal or increased cardiac sympathetic modulation, with alterations persisting until the following morning. These findings imply a dose-response relationship with potential for optimization of performance.

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.

Passive bilateral leg cycling with concomitant regional circulatory occlusion for testing mechanoreflex\u2013metaboreflex interactions in humans

PurposeThe exercise pressor reflex (EPR) plays a fundamental role in physiological reactions to exercise in humans and in the pathophysiology of cardiovascular disorders. There is no “gold standard” method for EPR assessment; therefore, we propose a new protocol for testing interactions between the muscle mechanoreflex and metaboreflex (major components of EPR).MethodsThirty-four healthy subjects (mean age [± standard deviation] 24 ± 4 years, 22 men) were enrolled in the study. During the study, the hemodynamic and ventilatory parameters of these subjects were continuously monitored using our proposed assessment method. This assessment method consists of an initial 5-min rest period (baseline) followed by 5 min of passive cycling (PC) on an automated cycle ergometer (mechanoreceptor stimulation), after which tourniquet cuffs located bilaterally on the upper thighs are inflated for 3 min to evoke venous and arterial regional circulatory occlusion (CO) during PC (metaboreceptor stimulation). Deflation of the tourniquet cuffs is followed by a second 5 min of PC and finally by a 5-min recovery time. The control test comprises a 5-min rest period, followed by 3 min of CO only and a final 5-min recovery.ResultsMean arterial pressure (MAP) and minute ventilation (MV) increased significantly during PC (MAP: from 90 ± 9.3 to 95 ± 9.7 mmHg; MV: from 11.5 ± 2.5 to 13.5 ± 2.9 L/min; both p < 0.05) and again when CO was applied (MAP: from 95 ± 9.7 to 101 ± 11.0 mmHg; MV: from 13.5 ± 2.9 to 14.8 ± 3.8 L/min; both p < 0.05). In the control test there was a slight increase in MAP during CO (from 92 ± 10.5 to 94 ± 10.0 mmHg; p < 0.05) and no changes in the ventilatory parameters.ConclusionBilateral leg passive cycling with concomitant circulatory occlusion is a new, simple and effective method for testing interactions between the mechanoreflex and metaboreflex in humans.

Muscle Temperature During Exercise Under Whole-body Heating And Limb Heating Conditions

Prior studies suggest that moderate whole-body heating (WBH), which raises internal temperature (Tcore) ~0.6-1.0 deg C, alters the exercise pressor reflex. It is speculated that elevated muscle temperature (Tmuscle) alters the sensitivity of muscle afferents. However, less is known about the effects of passive WBH on the limb Tmuscle during exercise. PURPOSE: To determine limb Tmuscle during exercise under passive WBH and limb heating conditions. METHODS:Forearm Tmuscle was measured with a needle probe (thermocouple) in 8 healthy subjects (57 +- 3 yrs). Mean skin temperature (Tsk), Tcore (telemetric pill), the arm skin temperature (Tarmskin, not covered by suits), blood pressure (BP) and heart rate (HR) were measured during WBH with water perfused suits. After Tcore rose ~0.6 deg C, subjects performed a fatiguing handgrip exercise followed by post exercise circulatory occlusion (PECO). In a separate visit, the forearm was heated with a water perfused sleeve. After the Tmuscle rose ~1 deg C (i.e. similar to that seen during WBH), the exercise paradigm was repeated. RESULTS: Passive WBH significantly raised Tsk (3.2 +- 0.3 deg C), Tarmskin (1.9 +- 1.0 deg C), Tmuscle (0.96 +- 0.15 deg C) and HR. The increases in Tmuscle were positively correlated with the increases in Tcore (R = 0.75, P < 0.05). Limb heating raised Tmuscle (0.98 +- 0.11 deg C), Tarmskin (2.3 +- 0.6 deg C), and did not alter Tsk, Tcore or HR. There was no significant difference in the grip force, grip time, or the change in HR with handgrip between the trials. The increases in Tmuscle during the last min of grip (0.37 +- 0.07 vs. 0.92 +- 0.17 deg C, P < 0.03) and PECO (P = 0.01) were significantly lower during WBH than during the limb heating trial. CONCLUSION: Although local limb heating and WBH induced similar elevations in Tmuscle, the responses in Tmuscle to exercise were different between these two heating conditions. Supported by NIH R01 HL141198 (Li and Cui) and UL1 TR002014 (Sinoway), and AHA Award #15GRNT24480051 (Cui).

Ischemic Preconditioning Of Thigh Muscles: Number Of Proper Repetitions And Effectiveness

Ischemic preconditioning (IPC) was introduced after it was demonstrated that repetitions of short-term ischemia and reperfusion of coronary arteries can reduce the myocardial damage following prolonged ischemia (direct IPC). It was later shown that the IPC of coronary arteries also protects remote cardiac tissue not directly exposed to IPC (remote IPC). Several studies suggested that the IPC of a limb may protect remote organs against an ischemic incident. Because of the intermittent nature of blood flow during intense muscle actions, it was proposed that IPC prior to exercise could increase muscular performance. Although most of the prior exercise studies used an IPC protocol involving four cycles of 5-min circulatory occlusion followed by a 5-min reperfusion period, the optimal number of repetitions of IPC has been unknown. PURPOSE: We examined the effects of direct IPC on thigh strength and sought to determine the optimal repetitions of IPC for successful results. METHODS: In a randomized cross-over study, 12 healthy young males (19.8 ± 2.1 yrs, body mass index: 22.1 ± 2.7 kg/m2) performed maximal knee extension (Biodex System 3; New York, USA) of the right leg preceded by direct IPC at four different repetitions (1, 2, 3, and 4 sets) and a control intervention. One IPC consisted of 5-min circulatory occlusion by 1.3-times systolic blood pressure and 5-min reperfusion. RESULTS: There was no significant difference in the maximal voluntary torque of knee extension between the control and any number of repetitions of the IPC, as shown below.MVT, maximal voluntary torque; Nm, newton meter. Data are mean ± SD (n=12). CONCLUSIONS: These data indicate that direct IPC for the thigh muscles could not improve maximal strength regardless of the number of repetitions. The application of pre-exercise IPC for improving performance should be further carefully examined concerning the optimal protocol and its indications, such as exercise types and target muscles.