Sex-specific microvascular and hemodynamic responses to passive limb heating in young adults.

OBJECTIVE: We examined sex-specific microvascular reactivity and hemodynamic responses under conditions of augmented resting blood flow induced by passive heating compared to normal blood flow. METHODS: Thirty-eight adults (19 females) completed a vascular occlusion test (VOT) on two occasions preceded by rest with or without passive heating in a randomized, counterbalanced order. Skeletal muscle tissue oxygenation (StO2, %) was assessed with near-infrared spectroscopy (NIRS), and the rate of desaturation and resaturation as well as maximal StO2 (StO2max) and prolonged hypersaturation (area under the curve, StO2AUC) were quantified. Before the VOT, brachial artery blood flow (BABF), vascular conductance, and relative BABF (BABF normalized to forearm lean mass) were determined. Sex × condition ANOVAs were used. A p-value ≤.05 was considered statistically significant. RESULTS: Twenty minutes of heating increased BABF compared to the control (102.9 ± 28.3 vs. 36.0 ± 20.9 mL min-1; p < .01). Males demonstrated greater BABF than females (91.9 ± 34.0 vs. 47.0 ± 19.1 mL min-1; p < .01). There was no sex difference in normalized BABF. There were no significant interactions for NIRS-VOT outcomes, but heat did increase the rate of desaturation (-0.140 ± 0.02 vs. -0.119 ± 0.03% s-1; p < .01), whereas regardless of condition, males exhibited greater rates of resaturation and StO2max than females. CONCLUSIONS: These results suggest that blood flow is not the primary factor causing sex differences in NIRS-VOT outcomes.

Sex Differences in Cardiac Rehabilitation Outcomes.

Cardiovascular disease is a leading cause of morbidity and mortality in males and females in the United States and globally. Cardiac rehabilitation (CR) is recommended by the American Heart Association/American College of Cardiology for secondary prevention for patients with cardiovascular disease. CR participation is associated with improved cardiovascular disease risk factor management, quality of life, and exercise capacity as well as reductions in hospital admissions and mortality. Despite these advantageous clinical outcomes, significant sex disparities exist in outpatient phase II CR programming. This article reviews sex differences that are present in the spectrum of care provided by outpatient phase II CR programming (ie, from referral to clinical management). We first review CR participation by detailing the sex disparities in the rates of CR referral, enrollment, and completion. In doing so, we discuss patient, health care provider, and social/environmental level barriers to CR participation with a particular emphasis on those barriers that majorly impact females. We also evaluate sex differences in the core components incorporated into CR programming (eg, patient assessment, exercise training, hypertension management). Next, we review strategies to mitigate these sex differences in CR participation with a focus on automatic CR referral, female-only CR programming, and hybrid CR. Finally, we outline knowledge gaps and areas of future research to minimize and prevent sex differences in CR programming.

Muscle microvascular oxygen delivery limitations during the contraction phase of intermittent maximal effort contractions.

PURPOSE: The end-test torque (ETT) during intermittent maximal effort contractions reflects the highest contraction intensity at which a muscle metabolic steady-state can be attained. This study determined if ETT is the highest intensity at which the contraction phase of intermittent exercise does not limit the matching of microvascular oxygen delivery to muscle oxygen demand. METHODS: Microvascular oxygenation characteristics of the biceps brachii muscle were measured in sixteen young, healthy individuals (8M/8F, 22 ± 3 years, 80.9 ± 20.3 kg) by near-infrared spectroscopy during maximal effort elbow flexion under control conditions (CON) and with complete circulatory occlusion (OCC). RESULTS: Increases in total-[heme] were blunted during OCC compared to CON (225 ± 87 vs. 264 ± 88 µM, p < 0.001) but OCC did not elicit a compensatory increase in deoxygenated-[heme] at any timepoint (108 ± 62 vs. 101 ± 61 µM, p > 0.05). Deoxygenated-[heme] was significantly elevated during contraction, relative to relaxation, above ETT (107 ± 60 vs. 98.8 ± 60.5 µM, p < 0.001), but not at ETT (91.7 ± 54.1 vs. 98.4 ± 62.2 µM, p = 0.174). Total-[heme] was significantly reduced during contraction, relative to relaxation, at all contraction intensities during CON (p < 0.05) and OCC (p < 0.05). CONCLUSION: These data suggest that ETT may reflect the highest contraction intensity at which contraction-induced increases in intramuscular pressures do not limit muscle perfusion to a degree that requires further increases in fractional oxygen extraction (i.e., deoxygenated-[heme]) despite limited microvascular diffusive conductance (i.e., total-[heme]).

Sex differences in muscle contraction-induced limb blood flow limitations.

PURPOSE: To determined sex differences in absolute- and %-reductions in blood flow during intermittent muscular contractions as well as relationships between blood flow reductions and time to task failure (TTF). METHODS: Thirteen males (25 ± 4 years) and 13 females (22 ± 5 years) completed intermittent isometric trapezoidal forearm flexion at 50% maximal voluntary contraction until task failure. Doppler ultrasound was used to measure brachial artery blood flow (BABF) during the 12-s plateau phase and 12-s relaxation phase. RESULTS: Target torque was less in females than males (24 ± 5 vs. 42 ± 7 Nm; p < 0.001); however, TTF was not different between sexes (F: 425 ± 187 vs. M: 401 ± 158 s; p = 0.72). Relaxation-phase BABF at end-exercise was less in females than males (435 ± 161 vs. 937 ± 281 mL/min; p < 0.001) but contraction-phase BABF was not different (127 ± 46 vs. 190 ± 99 mL/min; p = 0.42). Absolute- and %-reductions in BABF by contraction were less in females than males (309 ± 146 vs. 747 ± 210 mL/min and 69 ± 10 vs. 80% ± 6%, respectively; both p < 0.01) and were associated with target torque independent of sex (r = 0.78 and 0.56, respectively; both p < 0.01). Absolute BABF reduction per target torque (mL/min/Nm) and TTF were positively associated in males (r = 0.60; p = 0.031) but negatively associated in females (r = - 0.61; p = 0.029). CONCLUSIONS: This study provides evidence that females incur less proportional reduction in limb blood flow from muscular contraction than males at a matched relative intensity suggesting females may maintain higher levels of muscle oxygen delivery and metabolite removal than males across the contraction-relaxation cycle of intermittent exercise.

Blood flow restriction increases necessary muscle excitation of the elbow flexors during a single high-load contraction.

PURPOSE: To investigate the effects of blood flow restriction (BFR) on electromyographic amplitude (EMGRMS)-force relationships of the biceps brachii (BB) during a single high-load muscle action. METHODS: Twelve recreationally active males and eleven recreationally active females performed maximal voluntary contractions (MVCs), followed by an isometric trapezoidal muscle action of the elbow flexors at 70% MVC. Surface EMG was recorded from the BB during BFR and control (CON) visits. For BFR, cuff pressure was 60% of the pressure required to completely occlude blood at rest. Individual b (slope) and a terms (gain) were calculated from the log-transformed EMGRMS-force relationships during the linearly increasing and decreasing segments of the trapezoid. EMGRMS during the steady force segment was normalized to MVC EMGRMS. RESULTS: For BFR, the b terms were greater during the linearly increasing segment than the linearly decreasing segment (p < 0.001), and compared to the linearly increasing segment for CON (p < 0.001). The a terms for BFR were greater during the linearly decreasing than linearly increasing segment (p = 0.028). Steady force N-EMGRMS was greater for BFR than CON collapsed across sex (p = 0.041). CONCLUSION: BFR likely elicited additional recruitment of higher threshold motor units during the linearly increasing- and steady force-segment. The differences between activation and deactivation strategies were only observed with BFR, such as the b terms decreased and the a terms increased for the linearly decreasing segment in comparison to the increasing segment. However, EMGRMS-force relationships during the linearly increasing- and decreasing-segments were not different between sexes during BFR and CON.

Blood flow restriction increases motor unit firing rates and input excitation of the biceps brachii during a moderate-load muscle action.

This study examined the effects of blood flow restriction (BFR) on motor unit (MU) behaviour of the biceps brachii (BB) during a single non-exhausting submaximal muscle action. Twenty adults performed maximal voluntary contractions (MVCs) of the elbow flexors, followed by an isometric trapezoidal muscle action at 40% MVC during BFR and control (CON) visits. Surface electromyographic signals recorded from the BB during the 40% MVCs were decomposed. Recruitment thresholds (RTs), MU action potential amplitudes (MUAPAMPS), initial firing rates (IFRs), mean firing rates (MFRs) at steady force, and normalized EMG amplitude (N-EMGRMS) were analysed. Y-intercepts and slopes were calculated for the MUAPAMP, IFR, and MFR vs. RT relationships. Y-intercepts for the IFR and MFR vs. RT relationships and N-EMGRMS increased during BFR (p < 0.05) collapsed across sex. The slopes for the IFR and MFR vs. RT relationships decreased during BFR (p < 0.05) collapsed across sex. The y-intercepts and slopes for the MUAPAMP vs. RT relationships were not different (p > 0.05) between treatments or sex. BFR during the 40% MVC increased IFRs, MFRs, and N-EMGRMS. However, the similar MUAPAMPS observed between treatments may suggest that a greater load is necessary to recruit additional MUs when performing a single submaximal short-duration muscle action with BFR.

Influence of Blood Flow Restriction on Neuromuscular Function and Fatigue During Forearm Flexion in Men.

ABSTRACT: Montgomery, TR Jr, Olmos, A, Sears, KN, Succi, PJ, Hammer, SM, Bergstrom, HC, Hill, EC, Trevino, MA, and Dinyer-McNeely, TK. Influence of blood flow restriction on neuromuscular function and fatigue during forearm flexion in men. J Strength Cond Res 38(7): e349-e358, 2024-To determine the effects of blood flow restriction (BFR) on the mean firing rate (MFR) and motor unit action potential amplitude (MUAPAMP) vs. recruitment threshold (RT) relationships during fatiguing isometric elbow flexions. Ten men (24.5 ± 4.0 years) performed isometric trapezoidal contractions at 50% maximum voluntary contraction to task failure with or without BFR, on 2 separate days. For BFR, a cuff was inflated to 60% of the pressure required for full brachial artery occlusion at rest. During both visits, surface electromyography was recorded from the biceps brachii of the dominant limb and the signal was decomposed. A paired-samples t test was used to determine the number of repetitions completed between BFR and CON. ANOVAs (repetition [first, last] × condition [BFR, CON]) were used to determine differences in MFR vs. RT and MUAPAMP vs. RT relationships. Subjects completed more repetitions during CON (12 ± 4) than BFR (9 ± 2; p = 0.012). There was no significant interaction (p > 0.05) between the slopes and y-intercepts during the repetition × condition interaction for MUAPAMP vs. MFR. However, there was a main effect of repetition for the slopes of the MUAPAMP vs. RT (p = 0.041) but not the y-intercept (p = 0.964). Post hoc analysis (collapsed across condition) indicated that the slopes of the MUAPAMP vs. RT during the first repetition was less than the last repetition (first: 0.022 ± 0.003 mv/%MVC; last: 0.028 ± 0.004 mv/%MVC; p = 0.041). Blood flow restriction resulted in the same amount of higher threshold MU recruitment in approximately 75% of the repetitions. Furthermore, there was no change in MFR for either condition, even when taken to task failure. Thus, BFR training may create similar MU responses with less total work completed than training without BFR.

A Moderate Blood Flow Restriction Pressure Does Not Affect Maximal Strength or Neuromuscular Responses.

ABSTRACT: Lubiak, SM, Lawson, JE, Gonzalez Rojas, DH, Proppe, CE, Rivera, PM, Hammer, SM, Trevino, MA, Dinyer-McNeely, TK, Montgomery, TR, Olmos, AA, Sears, KN, Bergstrom, HC, Succi, PJ, Keller, JL, and Hill, EC. A moderate blood flow restriction pressure does not affect maximal strength or neuromuscular responses. J Strength Cond Res XX(X): 000-000, 2024-The purpose of this study was to examine the acute effects of blood flow restriction (BFR) applied at 60% of total arterial occlusion pressure (AOP) on maximal strength. Eleven college-aged female subjects completed two testing sessions of maximal unilateral concentric, isometric, and eccentric leg extension muscle actions performed with and without BFR. Separate 3 (mode [isometric, concentric, eccentric]) × 2 (condition [BFR, no BFR]) × 2 (visit [2, 3]) repeated-measures analysis of variances were used to examine mean differences in maximal strength, neuromuscular function, rating of perceived exertion (RPE), and pain. For maximal strength (collapsed across condition and visit), isometric (128.5 ± 22.7 Nm) and eccentric (114.5 ± 35.4 Nm) strength were greater than concentric maximal strength (89.3 ± 22.3 Nm) (p < 0.001-0.041). Muscle excitation relative (%) to isometric non-BFR was greater during the concentric (108.6 ± 31.5%) than during the eccentric (86.7 ± 29.2%) (p = 0.045) assessments but not different than isometric (93.4 ± 17.9%) (p = 0.109) assessments, collapsed across condition and visit. For RPE, there was an interaction such that RPE was greater during non-BFR (4.3 ± 1.7) than during BFR (3.7 ± 1.7) (p = 0.031) during the maximal concentric strength assessments. Furthermore, during maximal strength assessments performed with BFR, isometric RPE (5.8 ± 1.9) was greater than concentric (3.7 ± 1.7) (p = 0.005) and eccentric (4.6 ± 1.9) (p = 0.009) RPE. Finally, pain was greater during the isometric (2.8 ± 2.1 au) than during the concentric (1.8 ± 1.5 au) (p = 0.016), but not eccentric, maximal strength assessments (2.1 ± 1.6 au) (p = 0.126), collapsed across condition and visit. The application of BFR at 60% AOP did not affect concentric, isometric, or eccentric maximal strength or neuromuscular function. Trainers, clinicians, and researchers can prescribe exercise interventions relative to a restricted (when using a moderate AOP) or nonrestricted assessment of maximal strength.

The acute effects of passive heating on endothelial function, muscle microvascular oxygen delivery, and expression of serum HSP90α.

Passive heating has been a therapeutic tool used to elevate core temperature and induce increases in cardiac output, blood flow, and shear stress. We aimed to determine the effects of a single bout of passive heating on endothelial function and serum heat shock protein 90α (HSP90α) levels in young, healthy subjects. 8 healthy subjects were recruited to participate in one bout of whole-body passive heating via immersion in a 40 °C hot tub to maintain a 1 °C increase in rectal temperature for 60 min. Twenty-four hours after heating, shear-rate corrected endothelium-dependent dilation increased (pre: 0.004 ± 0.002%SRAUC; post: 0.006 ± 0.003%SRAUC; p = 0.034) but serum [HSP90α] was not changed (pre: 36.7 ± 10.3 ng/mL; post: 40.6 ± 15.9 ng/mL; p = 0.39). Neither resting muscle O2 utilization (pre: 0.17 ± 0.11 mL O2 min-1 (100 g)-1; post: 0.14 ± 0.09 mL O2 min-1 (100 g)-1); p = 0.28) nor mean arterial pressure (pre: 74 ± 11 mmHg; post: 73 ± 11 mmHg; p = 0.79) were influenced by the heating intervention. Finally, time to peak after cuff release was significantly delayed for % O2 sat (TTPpre = 39 ± 8.9 s and TTPpost = 43.5 ± 8.2 s; p = 0.007) and deoxy-[heme] (TTPpre = 41.3 ± 18.1 s and TTPpost = 51.4 ± 16.3 s; p = 0.018), with no effect on oxy-[heme] (p = 0.19) and total-[heme] (p = 0.41). One bout of passive heating improved endothelium-dependent dilation 24 h later in young, healthy subjects. This data suggests that passive heat treatments may provide a simple intervention for improving vascular health.

Muscle oxygenation during normoxic and hypoxic cycling exercise in humans with high-affinity haemoglobin.

NEW FINDINGS: What is the central question of this study? Do humans with high-affinity haemoglobin (HAH) demonstrate attenuated skeletal muscle deoxygenation during normoxic and hypoxic exercise? What is the main finding and its importance? Examination of near-infrared spectroscopy-derived muscle oxygenation profiles suggests that fractional oxygen extraction is blunted during hypoxic exercise in humans with HAH compared with control subjects. However, muscle tissue oxygen saturation levels were higher in humans with HAH during exercise in normoxia compared with control subjects. These alterations in fractional oxygen extraction in humans with HAH might influence blood flow regulation and exercise capacity during hypoxia. ABSTRACT: Recently, researchers in our laboratory have shown that humans with genetic mutations resulting in high-affinity haemoglobin (HAH) demonstrate better maintained aerobic capacity and peak power output during hypoxic exercise versus normoxic exercise in comparison to humans with normal-affinity haemoglobin. However, the influence of HAH on tissue oxygenation within exercising muscle during normoxia and hypoxia is unknown. Therefore, we examined near-infrared spectroscopy-derived oxygenation profiles of the vastus lateralis during graded cycling exercise in normoxia and hypoxia among humans with HAH (n = 5) and control subjects with normal-affinity haemoglobin (n = 12). The HAH group elicited a blunted increase of deoxygenated haemoglobin + myoglobin during hypoxic exercise compared with the control group (P = 0.03), suggesting reduced fractional oxygen extraction in the HAH group. In addition, the HAH group maintained a higher level of muscle tissue oxygen saturation during normoxic exercise (HAH, 75 ± 4% vs. controls, 65 ± 3%, P = 0.049) and there were no differences between groups in muscle tissue oxygen saturation during hypoxic exercise (HAH, 68 ± 3% vs. controls, 68 ± 2%, P = 0.943). Overall, our results suggest that humans with HAH might demonstrate divergent patterns of fractional oxygen extraction during hypoxic exercise and elevated muscle tissue oxygenation during normoxic exercise compared with control subjects.

Influence of blood flow occlusion on muscular recruitment and fatigue during maximal-effort small muscle-mass exercise.

KEY POINTS: The heavy-to-severe intensity exercise threshold (i.e. critical force) distinguishes between steady-state and progressive metabolic and neuromuscular responses to exercise. High levels of skeletal muscle sensory feedback related to peripheral fatigue development are thought to restrict motor unit activation and limit exercise tolerance. Utilizing limb blood flow occlusion, we demonstrate that critical force reflects an oxygen-delivery-dependent balance between motor unit activation and peripheral fatigue development. Our findings suggest that mechanisms which determine the total force-producing capacity of exercising skeletal muscle are significantly altered during blood flow occlusion. These findings may have widespread implications for exercise tolerance in patient populations who experience partial vascular occlusion or altered neuromuscular reflexes. ABSTRACT: High levels of muscle sensory feedback restrict motor unit activation and limit exercise tolerance. The roles of muscle fatigue development and motor unit activation in determining the heavy- to severe-intensity threshold (critical force; CF) remain unclear. This study utilized blood flow occlusion (OCC) to determine relationships between muscle fatigue development and motor unit activation during the determination of CF. We hypothesized that (1) OCC would exacerbate peripheral fatigue development and increase the rate of motor unit deactivation, and (2) blood flow reperfusion (REP) would result in muscle recovery and re-recruitment of motor units despite continuous maximal effort, (3) resulting in an end-exercise force not different from CF. Seven young, healthy subjects performed maximal-effort rhythmic handgrip exercise for 5 min under control conditions (CON) and during OCC and REP. Peripheral fatigue development and motor unit activation were measured via electrical stimulation and electromyography, respectively, during each test. OCC resulted in significantly greater peripheral fatigue development than CON (54.3 ± 34.8%; P < 0.001). Motor unit deactivation was only observed during OCC (P < 0.001). REP resulted in significant peripheral recovery (P < 0.001) and the re-recruitment of motor units (P < 0.001) to levels not different from CON. While OCC resulted in a significantly greater reduction in force production compared to CON (65.7 ± 35.6%; P < 0.001), REP resulted in the restoration of maximal-effort force production (266 ± 19 N; P < 0.001) to levels not different from CF (276 ± 55 N). These data suggest that CF reflects an oxygen-delivery-dependent balance between motor unit activation and peripheral fatigue development. Furthermore, this study established that mechanisms which determine the total force-producing capacity of exercising skeletal muscle are altered during OCC.

Limb blood flow and muscle oxygenation responses during handgrip exercise above vs. below critical force.

This study compared the brachial artery blood flow (Q̇BA) and microvascular oxygen delivery responses during handgrip exercise above vs. below critical force (CF; the isometric analog of critical power). Q̇BA and microvascular oxygen delivery are important determinants of oxygen utilization and metabolite accumulation during exercise, both of which increase progressively during exercise above CF. However the Q̇BA and microvascular oxygen delivery responses above vs. below CF remain unknown. We hypothesized that Q̇BA, deoxygenated-heme (deoxy-[heme]; an estimate of microvascular fractional oxygen extraction), and total-heme concentrations (total-[heme]; an estimate of changes in microvascular hematocrit) would demonstrate physiological maximums above CF despite increases in exercise intensity. Seven men and six women performed 1) a 5-min rhythmic isometric-handgrip maximal-effort test (MET) to determine CF and 2) two constant target-force tests above (severe-intensity; S1 and S2) and two constant target-force tests below (heavy-intensity; H1 and H2) CF. CF was 189.3 ± 16.7 N (29.7 ± 1.6%MVC). At end-exercise, Q̇BA was greater for tests above CF (S1: 418 ± 147 mL/min; S2: 403 ± 137 mL/min) compared to tests below CF (H1: 287 ± 97 mL/min; H2: 340 ± 116 mL/min; all p < 0.05) but was not different between S1 and S2. Further, end-test Q̇BA during both tests above CF was not different from Q̇BA estimated at CF (392 ± 37 mL/min). At end-exercise, deoxy-[heme] was not different between tests above CF (S1: 150 ± 50 µM; S2: 155 ± 57 µM), but was greater during tests above CF compared to tests below CF (H1: 101 ± 24 µM; H2: 111 ± 21 µM; all p < 0.05). At end-exercise, total-[heme] was not different between tests above CF (S1: 404 ± 58 µM; S2: 397 ± 73 µM), but was greater during tests above CF compared to H1 (352 ± 58 µM; p < 0.01) but not H2 (371 ± 57 µM). These data suggest limb blood flow limitations exist and maximal levels of muscle microvascular oxygen delivery and extraction occur during exercise above, but not below, CF.

Microvascular blood flow during vascular occlusion tests assessed by diffuse correlation spectroscopy.

NEW FINDINGS: What is the central question of this study? What are the characteristics of the time courses of blood flow in the brachial artery and microvascular beds of the skin and skeletal muscle following transient ischaemia? What is the main finding and its importance? Skeletal muscle blood flow was significantly slower than the transient increase in the cutaneous tissue, suggesting mechanistic differences between cutaneous and muscular blood flow distribution after transient ischaemia. These results challenge the use of the cutaneous circulation as globally representative of vascular function. ABSTRACT: Vascular function can be assessed by measuring post-occlusion hyperaemic responses along the arterial tree (vascular occlusion test; VOT). It is currently unclear if responses are similar across vascular beds following cuff release, given potential differences in compliance. To examine this, we compared laser Doppler-derived blood flux in the cutaneous circulation (LDFcut ) and skeletal muscle microvascular blood flux (BFI) using diffuse correlation spectroscopy (DCS), to brachial artery blood flow (BABF) during VOT. We hypothesized that during a VOT following cuff release, (1) BFI response would be delayed compared to the brachial artery response, and (2) time to peak blood flux in the cutaneous vasculature would be slower than both brachial artery and skeletal muscle responses. Seven healthy men (26 ± 4 years) performed three trials of a brachial artery VOT protocol with 10 min of rest between trials. A combined DCS and near-infrared spectroscopy probe provided BFI and oxygenation characteristics (total-[haem]), respectively, of skeletal muscle. BABF was determined via Doppler ultrasound and microvascular cutaneous blood flux was determined via LDFcut . Following cuff release, time to peak of BFI (32.3 ± 6.0 s) was significantly longer than BABF (7.3 ± 2.5 s), LDFcut (10.0 ± 6.4 s) and total-[haem] (14.2 ± 8.3 s) (all P < 0.001). However, time to peak of BABF, LDFcut and total-[haem] were not significantly different (P > 0.05). These results suggest mechanistic differences in control of cutaneous and muscular blood flow distribution after transient ischaemia.

Cardiovascular consequences of the inspiratory muscle metaboreflex: effects of age and sex.

With inspiratory muscle metaboreflex activation, we hypothesized that, compared with their younger counterparts, older men and women would exhibit greater 1) increases in mean arterial pressure (MAP) and limb vascular resistance (LVR) and 2) decreases in limb blood flow (Q̇L) but 3) no sex differences would be present in older adults. Sixteen young adults [8 young men (YM) and 8 young women (YW), 18-24 yr] and 16 older adults [8 older men (OM) and 8 older women (OW), 60-73 yr] performed inspiratory resistive breathing tasks (IRBTs) at 2% and 65% of their maximal inspiratory pressure. During the IRBTs, breathing frequency was 20 breaths/min with a 50% duty cycle. At baseline and during the IRBTs, MAP was measured via automated oscillometry, Q̇L was determined via Doppler ultrasound, and LVR was calculated. The 65% IRBT led to significantly greater increases in MAP in OW (15.9 ± 8.1 mmHg) compared with YW (6.9 ± 1.4 mmHg) but not (P > 0.05) between OM (12.3 ± 5.7 mmHg) and YM (10.8 ± 5.7 mmHg). OW (-20.2 ± 7.2%) had greater (P < 0.05) decreases in Q̇L compared with YW (-9.4 ± 10.2%), but no significant differences were present between OM (-22.8 ± 9.7%) and YM (-22.7 ± 11.3%) during the 65% IRBT. The 65% IRBT led to greater (P < 0.05) increases in LVR in OW (48.2 ± 25.5%) compared with YW (19.7 ± 15.0%), but no differences (P > 0.05) existed among OM (54.4 ± 17.8%) and YM (47.1 ± 23.3%). No significant differences were present in MAP, Q̇L, or LVR between OM and OW. These data suggest that OW exhibit a greater inspiratory muscle metaboreflex compared with YW, whereas no differences between OM and YM existed. Finally, sex differences in the inspiratory muscle metaboreflex are not present in older adults.NEW & NOTEWORTHY Premenopausal women exhibit an attenuated inspiratory muscle metaboreflex compared with young men; however, it is unknown whether these sex differences are present in older adults. Older women exhibited a greater inspiratory muscle metaboreflex compared with premenopausal women, whereas no differences were present between older and younger men.

Sex differences in the cardiovascular consequences of the inspiratory muscle metaboreflex.

It is currently unknown whether sex differences exist in the cardiovascular consequences of the inspiratory muscle metaboreflex. We hypothesized that the activation of the inspiratory muscle metaboreflex will lead to less of an increase in mean arterial pressure (MAP) and limb vascular resistance (LVR) and less of a decrease in limb blood flow (Q̇L) in women compared with men. Twenty healthy men (n = 10, 23 ± 2 yr) and women (n = 10, 22 ± 3 yr) were recruited for this study. Subjects performed inspiratory resistive breathing tasks (IRBTs) at 2% or 65% of their maximal inspiratory mouth pressure (PIMAX). During the IRBTs, the breathing frequency was 20 breaths/min with a 50% duty cycle. At rest and during the IRBTs, MAP was measured via automated oscillometry, Q̇L was measured via Doppler ultrasound, and LVR was calculated. EMG was recorded on the leg to ensure no muscle contraction occurred. The 65% IRBT led to attenuated increases (P < 0.01) from baseline in women compared with men for MAP (W: 7.3 ± 2.0 mmHg; M: 11.1 ± 5.0 mmHg) and LVR (W: 17.7% ± 14.0%; M: 47.9 ± 21.0%), as well as less of a decrease (P < 0.01) in Q̇L (W: -7.5 ± 9.9%; M: -23.3 ± 10.2%). These sex differences in MAP, Q̇L, and LVR were still present in a subset of subjects matched for PIMAX The 2% IRBT resulted in no significant changes in MAP, Q̇L, or LVR across time or between men and women. These data indicate premenopausal women exhibit an attenuated inspiratory muscle metaboreflex compared with age-matched men.

Higher Work of Breathing During Exercise in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: It is unknown if pulmonary alterations in heart failure with preserved ejection fraction (HFpEF) impact respiratory mechanics during exercise. RESEARCH QUESTION: Are the operating lung volumes, work of breathing (Wb), and power of breathing (Pb) abnormal in patients with HFpEF during exercise? STUDY DESIGN AND METHODS: Patients with HFpEF (n = 8; median age, 71 years [interquartile range (IQR), 66-80 years]) and control participants (n = 9; median age, 68 years [IQR, 64-74 years]) performed incremental cycling to volitional exhaustion. Esophageal pressure, end-expiratory lung volume (EELV), inspiratory lung volume (EILV), and ventilatory variables were compared at similar absolute (30 and 50 L/min) and relative (45% of peak, 70% of peak, and 100% of peak) minute ventilation (V.E) during exercise. RESULTS: During exercise, EELVs were not different between patients with HFpEF and control participants (P > .13 for all). EILVs were lower in patients with HFpEF than control participants at 45% and 70% V.E peak (P < .03 for all). Dynamic lung compliance was lower in patients with HFpEF than control participants at 30 L/min, 50 L/min, 45% V.E peak, and 100% V.E peak (P < .04 for all). Compared with control participants, patients with HFpEF showed higher total Wb and Pb at 30 L/min (Wb: median, 1.08 J/L [IQR, 0.93-1.82 J/L] vs 0.52 J/L [IQR, 0.43-0.71 J/L]; Pb: median, 36 J/min [IQR, 30-59 J/min] vs 17 J/min [IQR, 11-23 J/min] and 50 L/min; Wb: median, 1.40 J/L [IQR, 1.27-1.68 J/L] vs 0.90 J/L [IQR, 0.74-1.05 J/L]; Pb: median, 73 J/min [IQR, 60-83 J/min] vs 45 J/min [IQR, 33-63 J/min]; P < .01 for all). At 30 and 50 L/min, inspiratory and expiratory resistive Wb and Pb were higher in patients with HFpEF than control participants (P < .04 for all). Total Wb was higher for patients with HFpEF than control participants at 45% of V.E peak (P = .02). Total Pb was higher for control participants than patients with HFpEF at 100% V.E peak because of higher inspiratory resistive Pb (P < .04 for both). INTERPRETATION: These data demonstrate the HFpEF syndrome is associated with pulmonary alterations eliciting a greater Pb during exercise resulting from greater inspiratory and expiratory resistive Pb.

Sex differences in the intensity-duration relationships of the severe- and extreme-intensity exercise domains.

Extreme-intensity exercise is described by W'ext (analogous to J' for isometric exercise) that is smaller than W' of severe-intensity exercise (W'sev) in males. Sex differences in exercise tolerance appear to diminish at near-maximal exercise, however, there is evidence of greater contributions of peripheral fatigue (i.e. potentiated twitch force; Qpot) in males during extreme-intensity exercise. Therefore, the current study tested the hypotheses that J'ext would not be different between males and females, however, males would exhibit a greater reduction in neuromuscular function (i.e. maximal voluntary contraction, MVC; Qpot) following extreme-intensity exercise. Seven males and 7 females completed three severe- (Tlim: 2-4 min, S3; 5-8 min, S2; 9-15 min, S1) and three extreme-intensity (70, 80, 90%MVC) knee-extension bouts. MVC and Qpot relative to baseline were compared at task failure and at 150 s of recovery. J'ext was significantly less than J'sev in males (2.4 ± 1.2kJ vs 3.9 ± 1.3kJ; p = 0.03) and females (1.6 ± 0.8kJ vs 2.9 ± 1.7kJ; p = 0.05); however, there were no sex differences in J'ext or J'sev. MVC (%Baseline) was greater at task failure following extreme-intensity exercise (76.5 ± 20.0% vs 51.5 ± 11.5% in males, 75.7 ± 19.4% vs 66.7 ± 17.4% in females), but was not different at 150 s of recovery (95.7 ± 11.8% in males, 91.1 ± 14.2% in females). Reduction in Qpot, however, was greater in males (51.9 ± 16.3% vs 60.6 ± 15.5%) and was significantly correlated with J'ext (r2 = 0.90, p < 0.001). Although there were no differences in the magnitude of J'ext, differences in MVC and Qpot are evidence of sex-specific responses and highlight the importance of appropriately characterizing exercise intensity regarding exercise domains when comparing physiological responses in males and females.Highlights We have previously shown evidence that extreme-intensity dynamic exercise is described by W'ext in males and smaller than W'sev. We currently tested for potential sex differences in J'ext (isometric analogue to W') and neuromuscular responses (i.e. maximal voluntary contraction, MVC; potentiated twitch force, Qpot) during extreme-intensity exercise.J'ext and extreme-intensity exercise tolerance was not different between males and females. The reduction in MVC was not different across extreme-intensity exercise across males and females, whereas the reduction in Qpot was greater in males following all extreme-intensity exercises, although not after exercise at 90%MVC.Together, although extreme-intensity exercise tolerance is not different, these data highlight differences in the contributing mechanisms of fatigue during severe- and extreme-intensity exercise between males and females.

The relationship between hemoglobin and [Formula: see text]: A systematic review and meta-analysis.

OBJECTIVE: There is widespread agreement about the key role of hemoglobin for oxygen transport. Both observational and interventional studies have examined the relationship between hemoglobin levels and maximal oxygen uptake ([Formula: see text]) in humans. However, there exists considerable variability in the scientific literature regarding the potential relationship between hemoglobin and [Formula: see text]. Thus, we aimed to provide a comprehensive analysis of the diverse literature and examine the relationship between hemoglobin levels (hemoglobin concentration and mass) and [Formula: see text] (absolute and relative [Formula: see text]) among both observational and interventional studies. METHODS: A systematic search was performed on December 6th, 2021. The study procedures and reporting of findings followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article selection and data abstraction were performed in duplicate by two independent reviewers. Primary outcomes were hemoglobin levels and [Formula: see text] values (absolute and relative). For observational studies, meta-regression models were performed to examine the relationship between hemoglobin levels and [Formula: see text] values. For interventional studies, meta-analysis models were performed to determine the change in [Formula: see text] values (standard paired difference) associated with interventions designed to modify hemoglobin levels or [Formula: see text]. Meta-regression models were then performed to determine the relationship between a change in hemoglobin levels and the change in [Formula: see text] values. RESULTS: Data from 384 studies (226 observational studies and 158 interventional studies) were examined. For observational data, there was a positive association between absolute [Formula: see text] and hemoglobin levels (hemoglobin concentration, hemoglobin mass, and hematocrit (P<0.001 for all)). Prespecified subgroup analyses demonstrated no apparent sex-related differences among these relationships. For interventional data, there was a positive association between the change of absolute [Formula: see text] (standard paired difference) and the change in hemoglobin levels (hemoglobin concentration (P<0.0001) and hemoglobin mass (P = 0.006)). CONCLUSION: These findings suggest that [Formula: see text] values are closely associated with hemoglobin levels among both observational and interventional studies. Although our findings suggest a lack of sex differences in these relationships, there were limited studies incorporating females or stratifying results by biological sex.

Neuromuscular recovery from severe- and extreme-intensity exercise in men and women.

Maximal voluntary contraction force (MVC), potentiated twitch force (Qpot), and voluntary activation (%VA) recover to baseline within 90 s following extreme-intensity exercise. However, methodological limitations mask important recovery kinetics. We hypothesized reductions in MVC, Qpot, and %VA at task failure following extreme-intensity exercise would be less than following severe-intensity exercise, and Qpot and MVC following extreme-intensity exercise would show significant recovery within 120 s but remain depressed following severe-intensity exercise. Twelve subjects (6 men) completed 2 severe-intensity (40, 50% MVC) and 2 extreme-intensity (70, 80% MVC) isometric knee-extension exercise bouts to task failure (Tlim). Neuromuscular function was measured at baseline, Tlim, and through 150 s of recovery. Each intensity significantly reduced MVC and Qpot compared with baseline. MVC was greater at Tlim (p < 0.01) and at 150 s of recovery (p = 0.004) following exercise at 80% MVC compared with severe-intensity exercise. Partial recovery of MVC and Qpot were detected within 150 s following Tlim for each exercise intensity; Qpot recovered to baseline values within 150 s of recovery following exercise at 80% MVC. No differences in %VA were detected pre- to post-exercise or across recovery for any intensity. Although further analysis showed sex-specific differences in MVC and Qpot, future studies should closely examine sex-dependent responses to extreme-intensity exercise. It is clear, however, that these data reinforce that mechanisms limiting exercise tolerance during extreme-intensity exercise recover quickly. Novelty: Severe- and extreme-intensity exercise cause independent responses in fatigue accumulation and the subsequent recovery time courses. Recovery of MVC and Qpot occurs much faster following extreme-intensity exercise in both men and women.