Relationship of Warfarin and Apixaban with Vascular Function in Patients with Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is associated with endothelial damage/dysfunction. Herein, we tested the hypothesis that brachial artery flow-mediated dilation (FMD) is superior in AF patients taking apixaban compared to warfarin. METHODS: AF patients on apixaban (n = 46; 67 [7] years; mean [standard deviation]; 15 women) and warfarin (n = 27; 73 [9] years (p < 0.01); 11 women) were recruited. Duplex Doppler ultrasound imaging was undertaken during baseline (2 min), cuff inflation (5 min), and following cuff deflation (3 min). FMD was defined as peak increase in brachial artery diameter following cuff deflation and analysed as percentage change in diameter, as a ratio of FMD, shear rate area under the curve (SRAUC; FMD-to-SRAUC), and using SRAUC as a covariate (FMDSR). RESULTS: Baseline artery diameter (4.96 [1.14] vs. 4.89 [0.88] mm), peak diameter (5.12 [1.17] vs. 5.14 [0.93] mm), and FMDSR (3.89 [3.62] vs. 4.80 [3.60] %) were not different between warfarin and apixaban (p > 0.05; analysis of covariance with age, CHA2DS2-VASc, years since AF diagnosis, number of diabetics, alcohol drinkers, and units of alcohol consumed per week as covariates). Stepwise multiple regression identified independent association of fibrillation, hypertension, and increased age with FMD. CONCLUSION: AF patients on warfarin and apixaban exhibit similar endothelium-dependent vasodilation. Increased blood pressure negatively impacts vasodilator capacity in AF patients.

Central and peripheral chemoreflexes in humans with treated hypertension.

Increased peripheral chemoreflex sensitivity is a pathogenic feature of human hypertension (HTN), while both central and peripheral chemoreflex sensitivities are reportedly augmented in animal models of HTN. Herein, we tested the hypothesis that both central and combined central and peripheral chemoreflex sensitivities are augmented in HTN. Fifteen HTN participants (68 ± 5 years; mean ± SD) and 13 normotensives (NT; 65 ± 6 years) performed two modified rebreathing protocols in which the partial pressure of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\rm{ETC}}{{\rm{O}}_2}}}$ ) progressively increased while the partial pressure of end-tidal oxygen was clamped at either 150 mmHg (isoxic hyperoxia; central chemoreflex activation) or 50 mmHg (isoxic hypoxia; combined central and peripheral chemoreflex activation). Ventilation ( V ̇ E ${\dot{V}}_{\rm{E}}$ ; pneumotachometer) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded, and ventilatory ( V ̇ E ${\dot{V}}_{\rm{E}}$ vs. P ETC O 2 ${P_{{\rm{ETC}}{{\rm{O}}_2}}}$  slope) and sympathetic (MSNA vs. P ETC O 2 ${P_{{\rm{ETC}}{{\rm{O}}_2}}}$ slope) chemoreflex sensitivities and recruitment thresholds (breakpoint) were calculated. Global cerebral blood flow (gCBF; duplex Doppler) was measured, and the association with chemoreflex responses was examined. Central ventilatory and sympathetic chemoreflex sensitivities were greater in HTN than NT (2.48 ± 1.33 vs. 1.58 ± 0.42 L min-1  mmHg-1 , P = 0.030: 3.32 ± 1.90 vs. 1.77 ± 0.62 a.u. mmHg-1 , P = 0.034, respectively), while recruitment thresholds were not different between groups. HTN and NT had similar combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities and recruitment thresholds. A lower gCBF was associated with an earlier recruitment threshold for V ̇ E ${\dot{V}}_{\rm{E}}$ (R2  = 0.666, P < 0.0001) and MSNA (R2  = 0.698, P = 0.004) during isoxic hyperoxic rebreathing. These findings indicate that central ventilatory and sympathetic chemoreflex sensitivities are augmented in human HTN and perhaps suggest that targeting the central chemoreflex may help some forms of HTN. KEY POINTS: In human hypertension (HTN) increased peripheral chemoreflex sensitivity has been identified as a pathogenic feature, and in animal models of HTN, both central and peripheral chemoreflex sensitivities are reportedly augmented. In this study, the hypothesis was tested that both central and combined central and peripheral chemoreflex sensitivities are augmented in human HTN. We observed that both central ventilatory and sympathetic chemoreflex sensitivities were augmented in HTN compared to age-matched normotensive controls, but no difference was found in the combined central and peripheral ventilatory and sympathetic chemoreflex sensitivities. During central chemoreflex activation, the ventilatory and sympathetic recruitment thresholds were lower in those with lower total cerebral blood flow. These results indicate a potential contributory role of the central chemoreceptors in the pathogenesis of human HTN and support the possibility that therapeutic targeting of the central chemoreflex may help some forms of HTN.

Carbon dioxide protects simulated driving performance during severe hypoxia.

PURPOSE: We sought to determine the effect of acute severe hypoxia, with and without concurrent manipulation of carbon dioxide (CO2), on complex real-world psychomotor task performance. METHODS: Twenty-one participants completed a 10-min simulated driving task while breathing room air (normoxia) or hypoxic air (PETO2 = 45 mmHg) under poikilocapnic, isocapnic, and hypercapnic conditions (PETCO2 = not manipulated, clamped at baseline, and clamped at baseline + 10 mmHg, respectively). Driving performance was assessed using a fixed-base motor vehicle simulator. Oxygenation in the frontal cortex was measured using functional near-infrared spectroscopy. RESULTS: Speed limit exceedances were greater during the poikilocapnic than normoxic, hypercapnic, and isocapnic conditions (mean exceedances: 8, 4, 5, and 7, respectively; all p ≤ 0.05 vs poikilocapnic hypoxia). Vehicle speed was greater in the poikilocapnic than normoxic and hypercapnic conditions (mean difference: 0.35 km h-1 and 0.67 km h-1, respectively). All hypoxic conditions similarly decreased cerebral oxyhaemoglobin and increased deoxyhaemoglobin, compared to normoxic baseline, while total hemoglobin remained unchanged. CONCLUSIONS: These findings demonstrate that supplemental CO2 can confer a neuroprotective effect by offsetting impairments in complex psychomotor task performance evoked by severe poikilocapnic hypoxia; however, differences in performance are unlikely to be linked to measurable differences in cerebral oxygenation.

Meta-analysis of variation in sport and exercise science: Examples of application within resistance training research.

Meta-analysis has become commonplace within sport and exercise science for synthesising and summarising empirical studies. However, most research in the field focuses upon mean effects, particularly the effects of interventions to improve outcomes such as fitness or performance. It is thought that individual responses to interventions vary considerably. Hence, interest has increased in exploring precision or personalised exercise approaches. Not only is the mean often affected by interventions, but variation may also be impacted. Exploration of variation in studies such as randomised controlled trials (RCTs) can yield insight into interindividual heterogeneity in response to interventions and help determine generalisability of effects. Yet, larger samples sizes than those used for typical mean effects are required when probing variation. Thus, in a field with small samples such as sport and exercise science, exploration of variation through a meta-analytic framework is appealing. Despite the value of embracing and exploring variation alongside mean effects in sport and exercise science, it is rarely applied to research synthesis through meta-analysis. We introduce and evaluate different effect size calculations along with models for meta-analysis of variation using relatable examples from resistance training RCTs.

Supervision during resistance training positively influences muscular adaptations in resistance-trained individuals.

This study compared the effects of supervised versus unsupervised resistance training (RT) on measures of muscle strength and hypertrophy in resistance-trained individuals. Thirty-six young men and women were randomly assigned to one of two experimental, parallel groups to complete an 8-week RT programme: One group received direct supervision for their RT sessions (SUP); the other group performed the same RT programme in an unsupervised manner (UNSUP). Programme variables were kept constant between groups. We obtained pre- and post-study assessments of body composition via multi-frequency bioelectrical impedance analysis (MF-BIA), muscle thickness of the upper and lower limbs via ultrasound, 1 repetition maximum (RM) in the back squat and bench press, isometric knee extension strength, and countermovement jump (CMJ) height. Results showed the SUP group generally achieved larger increases in muscle thickness for the triceps brachii, all sites of the rectus femoris, and the proximal region of the vastus lateralis. MF-BIA indicated increases in lean mass favoured SUP. Squat 1RM was greater for SUP; bench press 1RM and isometric knee extension were similar between conditions. CMJ increases modestly favoured UNSUP. In conclusion, our findings suggest that supervised RT promotes greater muscular adaptations and enhances exercise adherence in young, resistance-trained individuals.

Sex differences in the sympathetic neurocirculatory responses to chemoreflex activation.

The purpose of this study was to determine whether there are sex differences in the cardiorespiratory and sympathetic neurocirculatory responses to central, peripheral, and combined central and peripheral chemoreflex activation. Ten women (29 ± 6 years, 22.8 ± 2.4 kg/m2 : mean ± SD) and 10 men (30 ± 7 years, 24.8 ± 3.2 kg/m2 ) undertook randomized 5 min breathing trials of: room air (eucapnia), isocapnic hypoxia (10% oxygen (O2 ); peripheral chemoreflex activation), hypercapnic hyperoxia (7% carbon dioxide (CO2 ), 50% O2 ; central chemoreflex activation) and hypercapnic hypoxia (7% CO2 , 10% O2 ; central and peripheral chemoreflex activation). Control trials of isocapnic hyperoxia (peripheral chemoreflex inhibition) and hypocapnic hyperoxia (central and peripheral chemoreflex inhibition) were also included. Muscle sympathetic nerve activity (MSNA; microneurography), mean arterial pressure (MAP; finger photoplethysmography) and minute ventilation ( V̇$\dot{\rm{V}}$E ; pneumotachometer) were measured. Total MSNA (P = 1.000 and P = 0.616), MAP (P = 0.265) and V̇$\dot{\rm{V}}$E (P = 0.587 and P = 0.472) were not different in men and women during eucapnia and during isocapnic hypoxia. Women exhibited attenuated increases in V̇$\dot{\rm{V}}$E during hypercapnic hyperoxia (27.3 ± 6.3 vs. 39.5 ± 7.5 l/min, P < 0.0001) and hypercapnic hypoxia (40.9 ± 9.1 vs. 53.8 ± 13.3 l/min, P < 0.0001) compared with men. However, total MSNA responses were augmented in women (hypercapnic hyperoxia 378 ± 215 vs. 258 ± 107%, P = 0.017; hypercapnic hypoxia 607 ± 290 vs. 362 ± 268%, P < 0.0001). No sex differences in total MSNA, MAP or V̇$\dot{\rm{V}}$E were observed during isocapnic hyperoxia and hypocapnic hyperoxia. Our results indicate that young women have augmented sympathetic responses to central chemoreflex activation, which explains the augmented MSNA response to combined central and peripheral chemoreflex activation. KEY POINTS: Sex differences in the control of breathing have been well studied, but whether there are differences in the sympathetic neurocirculatory responses to chemoreflex activation between healthy women and men is incompletely understood. We observed that, compared with young men, young women displayed augmented increases in muscle sympathetic nerve activity during both hypercapnic hyperoxia (central chemoreflex activation) and hypercapnic hypoxia (central and peripheral chemoreflex activation) but had attenuated increases in minute ventilation. In contrast, no sex differences were found in either muscle sympathetic nerve activity or minute ventilation responses to isocapnic hypoxia (peripheral chemoreceptor stimulation). Young women have blunted ventilator, but augmented sympathetic responses, to central (hypercapnic hyperoxia) and combined central and peripheral chemoreflex activation (hypercapnic hypoxia), compared with young men. The possible causative association between the reduced ventilation and heightened sympathetic responses in young women awaits validation.

Hypobaric hypoxia and cardiac baroreflex sensitivity in young women.

We sought to determine the effects of prolonged moderate hypobaric hypoxia (HH) on cardiac baroreflex sensitivity (cBRS) in young women and whether these effects are a consequence of the reduced arterial oxygen (O2) tension and/or increased pulmonary ventilation in HH. We hypothesized that HH would reduce cBRS and that this effect would be counteracted by acute restoration of the inspiratory partial pressure of O2 ([Formula: see text]) and/or voluntary attenuation of pulmonary ventilation. Twelve healthy women (24.0 ± 4.2 yr) were studied before (day 0) and twice during a sojourn in a hypobaric chamber (∼8 h, day 1; 4 days, day 4) where barometric pressure corresponded to ∼3,500-m altitude. Minute ventilation (V̇e; pneumotachometer), heart rate (electrocardiogram), and arterial pressure (finger volume clamp method) were recorded. cBRS was calculated using transfer function analysis between systolic pressure and RR interval. Assessments were made during 1) spontaneous breathing and (in HH only), 2) controlled breathing (reducing V̇e by ∼1 to 2 L/min), and 3) breathing a hyperoxic gas mixture that normalized [Formula: see text]. During spontaneous breathing, HH decreased cBRS (12.5 ± 7.1, 8.9 ± 4.4, and 7.4 ± 3.0 ms/mmHg on days 0, 1, and 4, respectively; P = 0.018). The normalization of [Formula: see text] increased cBRS (10.6 ± 3.3 and 10.7 ± 6.1 ms/mmHg on days 1 and 4) in HH compared with values observed during spontaneous breathing (P < 0.001), whereas controlled breathing had no effect on cBRS (P = 0.708). These findings indicate that ongoing arterial chemoreflex activation by the reduced arterial O2 tension, independently of the hypoxic ventilatory response, reduces cBRS in young women exposed to extended HH.NEW & NOTEWORTHY We examined the effects of prolonged hypobaric hypoxia (corresponding to ∼3,500-m altitude) on cardiac baroreflex sensitivity (cBRS) in young women and investigated underlying mechanisms. We found that cBRS was reduced in hypoxia and that this reduction was attenuated by acute restoration of inspiratory oxygen partial pressure but not by volitional restraint of pulmonary ventilation. These findings help to elucidate the role of arterial chemoreflex mechanisms in the control of cBRS during hypobaric hypoxia in young women.

Effects of hypoxia and hyperoxia on venous capacity and compliance in healthy men and women.

Blood oxygen is an important modulator of arterial function, but its impact on peripheral venous function is incompletely understood. Herein, we sought to determine the effect of hypoxia and hyperoxia on venous capacity and compliance in the lower limb. In 16 healthy individuals (7 women; age: 28.3 ± 7.6 yr, mean ± SD), we assessed peripheral oxygen saturation ([Formula: see text]), the cross-sectional area (CSA) of the great saphenous vein (GSV; Doppler ultrasound), and calf volume (strain-gauge plethysmography) during a standard 60 mmHg thigh cuff inflation-deflation protocol. Separate trials were undertaken during breathing of room air, hypoxia [fraction in inspired oxygen ([Formula: see text]): 0.10], and hyperoxia ([Formula: see text]: 0.50), according to a single-blinded, randomized design. Lower limb pressure-CSA and pressure-volume relationships were modeled using a quadratic regression equation and compliance derived. [Formula: see text] was decreased by hypoxia (83.6 ± 5.6%) and increased by hyperoxia (98.7 ± 0.5%) compared with room air (96.4 ± 1.0%, P < 0.001). Compared with room air (17.0 ± 7.9 mm2), hypoxia decreased GSV CSA (13.4 ± 5.7 mm2, P < 0.001), whereas no change was observed with hyperoxia (17.1 ± 8.7 mm2, P = 0.883). GSV compliance derived from the pressure-CSA relationships was elevated approximately twofold with hyperoxia (-0.0061 ± 0.0046 a.u.) when compared with room air (-0.0029 ± 0.002 a.u., P = 0.027) and hypoxia (-0.0030 ± 0.0032 a.u., P = 0.007). No differences were observed in calf pressure-volume parameters with either hypoxia or hyperoxia (P > 0.05). Our data indicate that GSV capacity is reduced by hypoxia, and that GSV compliance is increased by hyperoxia, thus highlighting the often overlooked role of oxygen in the regulation of venous circulation.

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. ABSTRACT: 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 ( V̇E$\dot{V}_E$ ; pneumotachometer), dyspnoea ratings (0-10 Borg scale), mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR; electrocardiogram) were measured. V̇E$\dot{V}_E$ was higher in the FILD group at baseline and exercise increased V̇E$\dot{V}_E$ similarly in both groups. V̇E$\dot{V}_E$ remained elevated during PECO, but there was no between-group difference in the magnitude of this response (Δ V̇E$\dot{V}_E$ 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.

Impact of acute dynamic exercise and arterial shear rate modification on radial artery low-flow mediated constriction in young men.

PURPOSE: Leg cycling exercise acutely augments radial artery low-flow mediated constriction (L-FMC). Herein, we sought to determine whether this is associated with exercise-induced changes in arterial shear rate (SR). METHODS: Ten healthy and recreationally active young men (23 ± 2 years) participated in 30 min of incremental leg cycling exercise (50, 100, 150 Watts). Trials were repeated with (Exercise + WC) and without (Exercise) the use of a wrist cuff (75 mmHg) placed distal to the radial artery to increase local retrograde SR while reducing mean and anterograde SR. Radial artery characteristics were measured throughout the trial, and L-FMC and flow mediated dilatation (FMD) were assessed before and acutely (~ 10 min) after leg cycling. RESULTS: Exercise increased radial artery mean and anterograde SR, along with radial artery diameter, velocity, blood flow and conductance (P < 0.05). Exercise + WC attenuated the exercise-induced increase in mean and anterograde SR (P > 0.05) but also increased retrograde SR (P < 0.05). In addition, increases in radial artery blood flow and diameter were reduced during Exercise + WC (Exercise + WC vs. Exercise, P < 0.05). After Exercise, L-FMC was augmented (- 4.4 ± 1.4 vs. - 13.1 ± 1.6%, P < 0.05), compared to no change in L-FMC after Exercise + WC (- 5.2 ± 2.0 vs. - 3.0 ± 1.6%, P > 0.05). In contrast, no change in FMD was observed in either Exercise or Exercise + WC trials (P > 0.05). CONCLUSIONS: These findings indicate that increases in L-FMC following exercise are abolished by the prevention of increases radial artery diameter, mean and anterograde SR, and by elevation of retrograde SR, during exercise in young men.

Cycle ergometer training and resistance training similarly increase muscle strength in trained men.

The aim of this study was to compare two different maximal intensity exercise modality training protocols of similar durations on muscle strength, cardiorespiratory fitness, and lower limb composition in recreationally trained men. Twenty-five trained men (28.9 ± 5.6 years) were randomly divided into Cycle ergometer (4 sets of 30 seconds sprints) and Leg press (4 sets of 10-12 repetitions to momentary failure). Both groups trained three times a week for 5 weeks. Before and after the training period, the participants performed a 10-repetition maximum (10RM) test for knee extension, an incremental exercise test on a treadmill for time to exhaustion (TTE) and peak oxygen consumption (V˙O2peak) and underwent dual energy X-ray absorptiometry to assess lower limb composition. Knee extension 10RM and TTE increased in both groups with no statistically significant between group (p = 0.614 and p = 0.210). Only cycle ergometer group increased V˙O2peak (p = 0,012). For all lower limb composition outcomes, changes were minimal. The results suggest that 5 weeks of effort and duration matched exercise protocols using cycle ergometer training or leg press may produce similar strength adaptations.

Heart rate variability in patients with atrial fibrillation and hypertension.

BACKGROUND: Atrial fibrillation (AF) and hypertension are independently associated with impaired autonomic function determined using heart rate variability (HRV). As these conditions frequently co-exist, we sought to determine whether AF would worsen HRV in hypertensive patients. DESIGN: We studied HRV in AF (and hypertension) (n = 61) and hypertension control group (n = 33). The AF (and hypertension) group was subdivided into permanent AF (n = 30) and paroxysmal AF (n = 31) and re-studied. Time-domain, frequency-domain and nonlinear measures of HRV were determined. Permanent AF group (n = 30) was followed up after 8 weeks following optimisation of their heart rate and blood pressure (BP). RESULTS: Time-domain and nonlinear indices of HRV were higher in AF (and hypertension) group compared to hypertensive controls (P ≤ .01). Time-domain and nonlinear indices of HRV were higher in permanent AF group compared to paroxysmal AF (P ≤ .001). Permanent AF was an independent predictor of HRV on multivariable analysis (P = .006). Optimisation of heart rate and BP had no significant impact on HRV in permanent AF. CONCLUSIONS: AF, independent of hypertension, is characterised with marked HRV and is possibly related to vagal tone. HRV is higher in permanent AF compared to paroxysmal AF suggesting evident autonomic influence in the pathophysiology of permanent AF. Modulation of autonomic influence on cardiovascular system should be explored in future studies.

The middle cerebral artery blood velocity response to acute normobaric hypoxia occurs independently of changes in ventilation in humans.

NEW FINDINGS: What is the central question of this study? Does the ventilatory response to moderate acute hypoxia increase cerebral perfusion independently of changes in arterial oxygen tension in humans? What is the main finding and its importance? The ventilatory response does not increase middle cerebral artery mean blood velocity during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation. ABSTRACT: Hypoxia induces ventilatory, cardiovascular and cerebrovascular adjustments to defend against reductions in systemic oxygen delivery. We aimed to determine whether the ventilatory response to moderate acute hypoxia increases cerebral perfusion independently of changes in arterial oxygenation. Eleven young healthy individuals were exposed to four 15 min experimental conditions: (1) normoxia (partial pressure of end-tidal oxygen, PETO2  = 100 mmHg), (2) hypoxia ( PETO2  = 50 mmHg), (3) normoxia with breathing volitionally matched to levels observed during hypoxia (hyperpnoea; PETO2  = 100 mmHg) and (4) hypoxia ( PETO2  = 50 mmHg) with respiratory frequency and tidal volume volitionally matched to levels observed during normoxia (i.e., restricted breathing (RB)). Isocapnia was maintained in all conditions. Middle cerebral artery mean blood velocity (MCA Vmean ), assessed by transcranial Doppler ultrasound, was increased during hypoxia (58 ± 12 cm/s, P = 0.04) and hypoxia + RB (61 ± 14 cm/s, P < 0.001) compared to normoxia (55 ± 11 cm/s), while it was unchanged during hyperpnoea (52 ± 13 cm/s, P = 0.08). MCA Vmean was not different between hypoxia and hypoxia + RB (P > 0.05). These findings suggest that the hypoxic ventilatory response does not increase cerebral perfusion, indexed using MCA Vmean , during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation.

Sympathetic regulation of coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in men.

NEW FINDINGS: What is the central question of this study? What is the role of ß- and α-adrenergic receptors in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans? What is the main finding and its importance? ß-Adrenergic receptor, but not α-adrenergic receptor, blockade significantly blunted the increases in coronary blood velocity observed during handgrip. Coronary blood velocity was unchanged from baseline during isolated muscle metaboreflex activation. This highlights the important role of ß-adrenergic receptors in the coronary circulation during handgrip in humans, and the more limited involvement of the α-adrenergic receptors. ABSTRACT: We sought to investigate the role of ß- and α-adrenergic receptors in coronary circulation during static handgrip exercise and isolated muscle metaboreflex activation in humans. Seventeen healthy young men underwent two experimental sessions, consisting of 3 min of static handgrip exercise at a target force of 40% maximum voluntary force (not achieved for the full 3 min), and 3 min of metaboreflex activation (post-exercise ischaemia) in two conditions: (1) control and ß-blockade (oral propranolol), and (2) control and α-blockade (oral prazosin). In both sessions, coronary blood velocity (CBV, echocardiography) was increased during handgrip (Δ8.0 ± 7.4 cm s-1 ) but unchanged with metaboreflex activation (Δ2.5 ± 3.2 cm s-1 ) under control conditions. ß-Blockade abolished the increase in CBV during handgrip, while CBV was unchanged from control with α-blockade. Cardiac work, estimated from rate pressure product (RPP; systolic blood pressure multiplied by heart rate), increased during handgrip and metaboreflex in control conditions in both sessions. ß-Blockade reduced RPP responses to handgrip and metaboreflex, whereas α-blockade increased RPP, but the responses to handgrip and metaboreflex were unchanged. CBV and RPP were only significantly correlated during handgrip under control (r = 0.71, P < 0.01) and ß-blockade (r = 0.54, P = 0.03) conditions, and the slope of this relationship was unaltered with ß-blockade. Collectively, these findings indicate that ß-adrenergic receptors play the primary role to the increase of coronary circulation during handgrip exercise, but CBV is unchanged with metaboreflex activation, while α-adrenergic receptor stimulation seems to exert no effect in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans.

Clinical utility of ventilatory and gas exchange evaluation during low-intensity exercise for risk stratification and prognostication in pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: Peak oxygen consumption (pVO2 ), determined from CPET, provides a valuable indication of PAH severity and patient prognosis. However, CPET is often contraindicated in severe PAH and frequently terminated prior to achievement of a sufficient exercise effort. We sought to determine whether in PAH low-intensity [i.e. freewheeling exercise (FW)] exercise reveals abnormal VE /VCO2 and PET CO2 responses that are associated with pVO2 and serve as indices of PAH risk stratification and mortality. METHODS: Retrospective analysis of CPET from 97 PAH patients and 20 age-matched controls was undertaken. FW VE /VCO2 and PET CO2 were correlated with pVO2 % age-predicted. Prognostication analysis was conducted using pVO2 > 65% age-predicted, as known to represent a low mortality risk. Primary outcome was mortality from any cause. RESULTS: FW PET CO2 was correlated with pVO2 (P < 0.0001; r = 0.52), while FW VE /VCO2 was not (P = 0.13; r = -0.16). ROC curve analyses showed that FW PET CO2 (AUC = 0.659), but not FW VE /VCO2 (AUC = 0.587), provided predictive information identifying pVO2 > 65% age-predicted (best cut-off value of 28 mm Hg). By Cox analysis, FW PET CO2 < 28 mm Hg remained a predictor of mortality after adjusting for age and PAH aetiology (HR: 2.360, 95% CI: 1.144-4.866, P = 0.020). CONCLUSION: Low PET CO2 during FW is associated with reduced pVO2 in PAH and provides predictive information for PAH risk stratification and prognostication.

Comparison of Isolated Lumbar Extension Strength in Competitive and Noncompetitive Powerlifters, and Recreationally Trained Men.

ABSTRACT: Androulakis-Korakakis, P, Gentil, P, Fisher, JP, and Steele, J. Comparison of isolated lumbar extension strength in competitive and noncompetitive powerlifters, and recreationally trained men. J Strength Cond Res 35(3): 652-658, 2021-Low-back strength has been shown to significantly impact performance in a plethora of sports. Aside from its effect on sport performance, low-back strength is strongly associated with low-back pain. A sport that heavily involves the lower-back musculature is powerlifting. This study looked to compare isolated lumbar extension (ILEX) strength in competitive and noncompetitive powerlifters, and recreationally trained men. Thirteen competitive powerlifters (CPL group; 31.9 ± 7.6 years; 173.4 ± 5.5 cm; 91.75 ± 18.7 kg), 10 noncompetitive powerlifters (NCPL group; 24 ± 3.5 years; 179 ± 4.8 cm; 92.39 ± 15.73 kg), and 36 recreationally trained men (RECT group; 24.9 ± 6.5 years; 178.5 ± 5.2 cm; 81.6 ± 10.0 kg) were tested for ILEX. Isolated lumbar extension strength was measured at every 12° throughout subject's full range of motion (ROM) and expressed as the following: "strength index (SI)" calculated as the area under a torque curve from multiple angle testing, average torque produced across each joint angle (AVG), and maximum torque produced at a single angle (MAX). Deadlift and squat strength were measured using 1 repetition maximum for the competitive and noncompetitive powerlifters. The following powerlifting characteristics were recorded for the competitive and noncompetitive powerlifters: primary deadlift stance, primary squat bar position, use of belt, use of performance-enhancing drugs, and use of exercises to target the lower-back musculature. Significant between-group effects were found for subject characteristics (age, stature, body mass, and ROM). However, analysis of covariance with subject characteristics as covariates found no significant between-group effects for SI (p = 0.824), AVG (p = 0.757), or MAX (p = 0.572). In conclusion, this study suggests that powerlifting training likely has little impact on conditioning of the lumbar extensors.

Resistance Training Performed to Failure or Not to Failure Results in Similar Total Volume, but With Different Fatigue and Discomfort Levels.

ABSTRACT: Santos, WDNd, Vieira, CA, Bottaro, M, Nunes, VA, Ramirez-Campillo, R, Steele, J, Fisher, JP, and Gentil, P. Resistance training performed to failure or not to failure results in similar total volume, but with different fatigue and discomfort levels. J Strength Cond Res 35(5): 1372-1379, 2021-The purpose of this study was to compare the acute response to 4 sets of high velocity parallel squats performed to momentary failure (MF) or not to momentary failure (NF). Twelve women (24.93 ± 5.04 years) performed MF and NF protocols, in a randomized order with 2-3 interday rest. The protocol involved 4 sets of parallel squats executed at high velocity at 10RM load, with 2 minutes of rest interval between sets. During the NF protocol, the sets were interrupted when the subject lost more than 20% of mean propulsive velocity. The analysis involved the number of repetitions performed per set, total number of repetitions, movement velocity loss, power output loss, rating of perceived exertion (RPE), rating of perceived discomfort (RPD), and session rating of perceived exertion (sRPE). Compared with NF, MF resulted in a higher number of repetitions in the first set (11.58 ± 1.83 vs. 7.58 ± 1.72, p < 0.05), but a lower in the last set (3.58 ± 1.08 vs. 5.41 ± 1.08, p < 0.05). Total number of repetitions was similar between the protocols (MF 26.25 ± 3.47 vs. NF 24.5 ± 3.65, p > 0.05). In both protocols, there were significant decreases in maximum and mean movement velocity loss and power output loss, but higher decreases were observed in MF than NF (p < 0.05). Values for RPE, sRPE, and RPD were higher during MF than NF (p < 0.05). Controlling the movement velocity in NF protocol enabled performance of a similar total volume of repetitions with lower movement velocity and power output losses, RPE, sRPE, and RPD than during an MF protocol.

The Logic of Carotid Body Connectivity to the Brain.

The carotid body has emerged as a therapeutic target for cardio-respiratory-metabolic diseases. With the expansive functions of the chemoreflex, we sought mechanisms to explain differential control of individual responses. We purport a remarkable correlation between phenotype of a chemosensory unit (glomus cell-sensory afferent) with a distinct component of the reflex response. This logic could permit differential modulation of distinct chemoreflex responses, a strategy ideal for therapeutic exploitation.

Cerebrovascular carbon dioxide reactivity and flow-mediated dilation in young healthy South Asian and Caucasian European men.

South Asians living in the United Kingdom have a 1.5-fold greater risk of ischemic stroke than the general population. Impaired cerebrovascular carbon dioxide (CO2) reactivity is an independent predictor of ischemic stroke and cardiovascular mortality. We sought to test the hypothesis that cerebrovascular CO2 reactivity is reduced in South Asians. Middle cerebral artery blood velocity (MCA Vm) was measured at rest and during stepwise changes in end-tidal partial pressure of CO2 (PETCO2) in South Asian (n = 16) and Caucasian European (n = 18) men who were young (~20 yr), healthy, and living in the United Kingdom. Incremental hypercapnia was delivered via the open-circuit steady-state method, with stages of 4 and 7% CO2 (≈21% oxygen, nitrogen balanced). Cerebrovascular CO2 reactivity was calculated as the change in MCA Vm relative to the change in PETCO2. MCA Vm was not different in South Asians [59 (9) cm/s, mean (standard deviation)] and Caucasian Europeans [61 (12) cm/s; P > 0.05]. Similarly, cerebrovascular CO2 reactivity was not different between the groups [South Asian 2.53 (0.76) vs. Caucasian European 2.61 (0.81) cm·s-1·mmHg-1; P > 0.05]. Brachial artery flow-mediated dilation was lower in South Asians [5.48 (2.94)%] compared with Caucasian Europeans [7.41 (2.28)%; P < 0.05]; however, when corrected for shear rate no between-group differences in flow-mediated dilation were observed (P > 0.05). Flow-mediated dilation was not correlated with cerebrovascular CO2 reactivity measures. In summary, cerebrovascular CO2 reactivity and flow-mediated dilation corrected for shear rate are preserved in young healthy South Asian men living in the United Kingdom.NEW & NOTEWORTHY Previous reports have identified an increased risk of ischemic stroke and peripheral endothelial dysfunction in South Asians compared with Caucasian Europeans. The main finding of this study is that cerebrovascular carbon dioxide reactivity (an independent predictor of ischemic stroke) is not different in healthy young South Asian and Caucasian European men.

Neurovascular coupling is not influenced by lower body negative pressure in humans.

Cerebral blood flow is tightly coupled with local neuronal activation and metabolism, i.e., neurovascular coupling (NVC). Studies suggest a role of sympathetic nervous system in the regulation of cerebral blood flow. However, this is controversial, and the sympathetic regulation of NVC in humans remains unclear. Since impaired NVC has been identified in several chronic diseases associated with a heightened sympathetic activity, we aimed to determine whether reflex-mediated sympathetic activation via lower body negative pressure (LBNP) attenuates NVC in humans. NVC was assessed using a visual stimulation protocol (5 cycles of 30 s eyes closed and 30 s of reading) in 11 healthy participants (aged 24 ± 3 yr). NVC assessments were made under control conditions and during LBNP at -20 and -40 mmHg. Posterior (PCA) and middle (MCA) cerebral artery mean blood velocity (Vmean) and vertebral artery blood flow (VAflow) were simultaneously determined with cardiorespiratory variables. Under control conditions, the visual stimulation evoked a robust increase in PCAVmean (∆18.0 ± 4.5%), a moderate rise in VAflow (∆9.6 ± 4.3%), and a modest increase in MCAVmean (∆3.0 ± 1.9%). The magnitude of NVC response was not affected by mild-to-moderate LBNP (all P > 0.05 for repeated-measures ANOVA). Given the small change that occurred in partial pressure of end-tidal CO2 during LBNP, this hypocapnia condition was matched via voluntary hyperventilation in absence of LBNP in a subgroup of participants (n = 8). The mild hypocapnia during LBNP did not exert a confounding influence on the NVC response. These findings indicate that the NVC is not influenced by LBNP or mild hypocapnia in humans.NEW & NOTEWORTHY Visual stimulation evoked a robust increase in posterior cerebral artery velocity and a modest increase in vertebral artery blood flow, i.e., neurovascular coupling (NVC), which was unaffected by lower body negative pressure (LBNP) in humans. In addition, although LBNP induced a mild hypocapnia, this degree of hypocapnia in the absence of LBNP failed to modify the NVC response.