Reflex sympathetic activation to inspiratory muscle loading is attenuated in females relative to males.

Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males (n = 9) and females (n = 7) completed two experimental days. On day 1, participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency (P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task (P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation.NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

Assessing Leg Blood Flow and Cardiac Output During Running Using Thermodilution.

Cardiac output (Q̇C) and leg blood flow (Q̇LEG) can be measured simultaneously with high accuracy using transpulmonary and femoral vein thermodilution with a single-bolus injection. The invasive measure has offered important insight into leg hemodynamics and blood flow distribution during exercise. Despite being the natural modality of exercise in humans, there has been no direct measure of Q̇LEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring Q̇LEG and conductance during high-intensity running, in an exploratory case study. A trained runner (30 years male) completed two maximal incremental tests on a cycle ergometer and motorized treadmill. Q̇LEG and Q̇C were determined using the single-bolus thermodilution technique. Arterial and venous blood were sampled throughout exercise, with continuous monitoring of metabolism, intra-arterial and venous pressure, and temperature. The participant reached a greater peak oxygen uptake (V̇O2peak) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable Q̇LEG (19.0 vs. 19.5 L/min) and Q̇C (27.4 vs. 26.2 L/min). Leg vascular conductance was greater during high-intensity running relative to cycling (82 vs. 70 mL/min/mmHg @ ~80% V̇O2peak). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% V̇O2peak). In summary, we present the first direct measure of Q̇LEG and conductance in a running human. Our findings corroborate several assumptions about Q̇LEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely.

The Effect of Waistbands on Intra-Abdominal Pressure and Respiratory Mechanics During Bodyweight Exercise.

ABSTRACT: Leahy, MG, Kipp, S, and Sheel, AW. The effect of waistbands on intra-abdominal pressure and respiratory mechanics during bodyweight exercise. J Strength Cond Res XX(X): 000-000, 2024-Athletic apparel is often designed with high-waisted, elastic bands around the abdomen to provide comfort and support during functional exercises. The abdominal musculature aids in both active respiration and trunk stability during the exercise, but whether high-waistband athletic garments affect pulmonary function and respiratory mechanics is unknown. Ten healthy women participated in a single-visit study. Subjects were fitted with esophageal and gastric balloon-tipped catheters and completed three bouts of isometric and dynamic bodyweight squats, lunges, and planks, during which ventilation and pulmonary pressures were continuously recorded. Resting pulmonary function was unchanged by high-waistband garments. During isometric squatting exercise, peak abdominal pressure was significantly greater while wearing high-waistband garments (17 ± 6 cmH2O), relative to low-waistband garments (15 ± 6 cmH2O, p = 0.032). The work of breathing was reduced when completing dynamic squat exercise in a high-waistband garment (16.2 ± 3.9 J·min-1), relative to a low-waistband garment (18.6 ± 5.7 J·min-1, p = 0.026). High waistbands had no effect on abdominal pressures or pulmonary mechanics during lunge or plank exercises. We believe our findings indicate that high-waistband garments have the capacity to alter abdominal and ventilatory mechanics during bodyweight squatting exercises but are unlikely to have an effect during other exercise movements.

Effects of sex and ageing on the human respiratory muscle metaboreflex.

Intense inspiratory muscle work evokes a sympathetically mediated pressor reflex, termed the respiratory muscle metaboreflex, in which young females demonstrate an attenuated response relative to males. However, the effects of ageing and female sex hormones on the respiratory muscle metaboreflex are unclear. We tested the hypothesis that the pressor response to inspiratory work would be similar between older males and females, and higher relative to their younger counterparts. Healthy, normotensive young (26 ± 3 years) males (YM; n = 10) and females (YF; n = 10), as well as older (64 ± 5 years) males (OM; n = 10) and females (OF; n = 10), performed inspiratory pressure threshold loading (PTL) to task failure. Older adults had a greater mean arterial pressure (MAP) response to PTL than young (P < 0.001). YF had a lower MAP compared to YM (+10 ± 6 vs. +19 ± 15 mmHg, P = 0.026); however, there was no difference observed between OF and OM (+26 ± 11 vs. +27 ± 11 mmHg, P = 0.162). Older adults had a lower heart rate response to PTL than young (P = 0.002). There was no effect of sex between young females and males (+19 ± 9 and +27 ± 11 bpm, P = 0.186) or older females and males (+17 ± 7 and +20 ± 7 bpm, P = 0.753). We conclude the respiratory muscle metaboreflex response is heightened in older adults, and the sex effect between older males and post-menopause females is absent, suggesting an effect of circulating sex hormones. KEY POINTS: The arterial blood pressure response to the respiratory muscle metaboreflex is greater in older males and females. Compared to sex-matched young individuals, there is no sex differences in the blood pressure response between older males and post-menopause females. Our results suggest the differences between males and females in the cardiovascular response to high levels of inspiratory muscle work is abolished with reduced circulating female sex hormones.

The effect of proportional assist ventilation on the electrical activity of the human diaphragm during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease. ABSTRACT: We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMGdi ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure-time product of the diaphragm (PTPdi ) was lower across PAV unloading conditions (P < 0.05). The EMGdi was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMGdi with PAV unloading were 14, 22 and 39%, respectively. The change in EMGdi for a given lowering of PTPdi with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease.

Correlation of Immunological and Molecular Profiles with Response to Crizotinib in Alveolar Soft Part Sarcoma: An Exploratory Study Related to the EORTC 90101 "CREATE" Trial.

Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma characterized by an unbalanced translocation, resulting in ASPSCR1-TFE3 fusion that transcriptionally upregulates MET expression. The European Organization for Research and Treatment of Cancer (EORTC) 90101 "CREATE" phase II trial evaluated the MET inhibitor crizotinib in ASPS patients, achieving only limited antitumor activity. We performed a comprehensive molecular analysis of ASPS tissue samples collected in this trial to identify potential biomarkers correlating with treatment outcome. A tissue microarray containing 47 ASPS cases was used for the characterization of the tumor microenvironment using multiplex immunofluorescence. DNA isolated from 34 available tumor samples was analyzed to detect recurrent gene copy number alterations (CNAs) and mutations by low-coverage whole-genome sequencing and whole-exome sequencing. Pathway enrichment analysis was used to identify diseased-associated pathways in ASPS sarcomagenesis. Kaplan-Meier estimates, Cox regression, and the Fisher's exact test were used to correlate histopathological and molecular findings with clinical data related to crizotinib treatment, aiming to identify potential factors associated with patient outcome. Tumor microenvironment characterization showed the presence of PD-L1 and CTLA-4 in 10 and 2 tumors, respectively, and the absence of PD-1 in all specimens. Apart from CD68, other immunological markers were rarely expressed, suggesting a low level of tumor-infiltrating lymphocytes in ASPS. By CNA analysis, we detected a number of broad and focal alterations. The most common alteration was the loss of chromosomal region 1p36.32 in 44% of cases. The loss of chromosomal regions 1p36.32, 1p33, 1p22.2, and 8p was associated with shorter progression-free survival. Using whole-exome sequencing, 13 cancer-associated genes were found to be mutated in at least three cases. Pathway enrichment analysis identified genetic alterations in NOTCH signaling, chromatin organization, and SUMOylation pathways. NOTCH4 intracellular domain dysregulation was associated with poor outcome, while inactivation of the beta-catenin/TCF complex correlated with improved outcome in patients receiving crizotinib. ASPS is characterized by molecular heterogeneity. We identify genetic aberrations potentially predictive of treatment outcome during crizotinib therapy and provide additional insights into the biology of ASPS, paving the way to improve treatment approaches for this extremely rare malignancy.

An integrative approach to the pulmonary physiology of exercise: when does biological sex matter?

Historically, many studies investigating the pulmonary physiology of exercise (and biomedical research in general) were performed exclusively or predominantly with male research participants. This has led to an incomplete understanding of the pulmonary response to exercise. More recently, important sex-based differences with respect to the human respiratory system have been identified. The purpose of this review is to summarize current findings related to sex-based differences in the pulmonary physiology of exercise. To that end, we will discuss how morphological sex-based differences of the respiratory system affect the respiratory response to exercise. Moreover, we will discuss sex-based differences of the physiological integrative responses to exercise, and how all these differences can influence the regulation of breathing. We end with a brief discussion of pregnancy and menopause and the accompanying ventilatory changes observed during exercise.

Near-infrared spectroscopy measures of sternocleidomastoid blood flow during exercise and hyperpnoea.

NEW FINDINGS: What is the central question of this study? How does sternocleidomastoid blood flow change in response to increasing ventilation and whole-body exercise intensity? What is the main finding and its importance? Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole-body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid. ABSTRACT: Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood-flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near-infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole-body exercise.

Diaphragm fatigue and inspiratory muscle metaboreflex in men and women matched for absolute diaphragmatic work during pressure-threshold loading.

KEY POINTS: The female diaphragm fatigues at a slower rate compared to that of males, with blunted cardiovascular consequences (i.e. inspiratory muscle metaboreflex). It is unclear if these findings are a function of relative or absolute diaphragmatic work. We asked if sex differences in diaphragm fatigue and the inspiratory muscle metaboreflex persisted during inspiratory loading performed at equal absolute intensities. We found that matching men and women for absolute diaphragmatic work resulted in an equal degree of diaphragm fatigue, despite women performing significantly greater work relative to body mass. Metabolite-induced reflex influences in sympathetic outflow originating from the diaphragm are attenuated in women, with potential implications for blood flow distribution during exercise. ABSTRACT: In response to inspiratory pressure-threshold loading (PTL), women have greater inspiratory muscle endurance time, slower rate of diaphragm fatigue development, and a blunted pressor response compared to men. It is unclear if these differences are due to discrepancies in absolute diaphragm force output. We tested the hypothesis that following inspirations performed at equal absolute intensities, females would develop a similar level of diaphragm fatigue and an attenuated cardiovascular response relative to men. Healthy young men (n = 8, age = 24 ± 3 years) and women (n = 8, age = 23 ± 3 years) performed PTL whilst targeting a transdiaphragmatic pressure (Pdi ) of 92 cmH2 O for 5 min. Diaphragm fatigue was assessed via twitch Pdi (Pdi,tw ) using cervical magnetic stimulation. Heart rate (HR) and mean arterial blood pressure were monitored continuously. During PTL, the absolute amount of diaphragm work was not different between men (13,399 ± 2019 cmH2 O s) and women (12,986 ± 1846 cmH2 O s; P > 0.05); however, women performed the PTL task at a higher relative P¯di /Pdi,max . Following inspiratory PTL, the magnitude of reduction in Pdi,tw was similar between men (-27.1 ± 7.2%) and women (-23.8 ± 13.8%; P > 0.05). There were significant increases in HR over time (P < 0.05), but this did not differ on the basis of sex (P > 0.05). Mean arterial blood pressure increased significantly over time in both men and women (P < 0.05); however, the rate of change was higher in men (6.24 ± 2.54 mmHg min-1 ) than in women (4.15 ± 2.52 mmHg min-1 ) (P < 0.05). We conclude that the female diaphragm is protected against severe fatigue when inspiratory work is excessive and as a result does not evoke overt sympathoexcitation.

Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial.

BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder. METHODS: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. FINDINGS: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0.78, 95% CI 0.56-1.08; p=0.13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0.54, 95% CI 0.4-0.73, p<0.0001), with 5-year progression-free survival of 47.6% (95% CI 38.8-55.9) in the immediate treatment group and 31.8% (24.2-39.6) in the deferred treatment group. Grade 3-4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group. INTERPRETATION: Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. FUNDING: Lilly, Canadian Cancer Society Research.

Sports Bra Restriction on Respiratory Mechanics during Exercise.

PURPOSE: We set out to understand how underband tightness or pressure of a sports bra relates to respiratory function and the mechanical work of breathing ( during exercise. Our secondary purpose was to quantify the effects of underband pressure on O 2 during submaximal running. METHODS: Nine highly trained female runners with normal pulmonary function completed maximal and submaximal running in three levels of underband restriction: loose, self-selected, and tight. RESULTS: During maximal exercise, we observed a significantly greater during the tight condition (350 ± 78 J·min -1 ) compared with the loose condition (301 ± 78 J·min -1 ; P < 0.05), and a 5% increase in minute ventilation ( ) during the tight condition compared with the loose condition ( P < 0.05). The pattern of breathing also differed between the two conditions; the greater maximal during the tight condition was achieved by a higher breathing frequency (57 ± 6 vs. 52 ± 7 breaths·min -1 ; P < 0.05), despite tidal volume being significantly lower in the tight condition compared with the loose condition (1.97 ± 0.20 vs. 2.05 ± 0.23 L; P < 0.05). During steady-state submaximal running, O 2 increased 1.3 ± 1.1% (range: -0.3 to 3.2%, P < 0.05) in the tight condition compared with the loose condition. CONCLUSIONS: Respiratory function may become compromised by the pressure exerted by the underband of a sports bra when women self-select their bra size. In the current study, loosening the underband pressure resulted in a decreased work of breathing, changed the ventilatory breathing pattern to deeper, less frequent breaths, and decreased submaximal oxygen uptake (improved running economy). Our findings suggest sports bra underbands can impair breathing mechanics during exercise and influence whole-body metabolic rate.

The human skeletal muscle metaboreflex contribution to cardiorespiratory control in males and females in dynamic exercise.

There is a significant effect of sex and muscle mass on the cardiorespiratory response to the skeletal muscle metaboreflex during isometric exercise. We therefore tested the hypothesis that sex differences would be present when isolated following dynamic exercise. We also tested the hypothesis that single and double leg post-exercise circulatory occlusion (PECO) following heavy exercise would elicit a cardiorespiratory response proportional to the absolute muscle mass. Healthy (24 ± 4 years) males (n = 10) and females (n = 10) completed pulmonary function and an incremental cycle test to exhaustion. Participants completed two randomized, 6 min bouts of intense cycle exercise (84 ± 7% V̇O2peak). One exercise bout was immediately followed by 3 min PECO (220 mmHg) of the legs while the other exercise bout was followed by passive recovery. Males completed an additional session of testing with single leg PECO. The mean arterial pressure during PECO and control was greater in males compared to females (p = 0.004). The was a significant time by condition by sex interaction in the heart rate response to PECO (p = 0.027). There was also a significant condition by sex interaction in the ventilatory response to PECO (p = 0.026). In males, we observed a dose-dependent cardiovascular, but not ventilatory, response to muscle mass occluded (all p < 0.05). Our findings suggest the metaboreflex contribution to cardiorespiratory control during dynamic exercise is greater in males compared to females. The ventilatory response induced by double-leg occlusion but not single-leg occlusion, suggests that the ventilatory influence of the metaboreflex is less sensitive than the cardiovascular response and may be linked to the greater afferent activation induced by double-leg occlusion.

The metabolic cost of breathing for exercise ventilations: effects of age and sex.

Given that there are both sex-based structural differences in the respiratory system and age-associated declines in pulmonary function, the purpose of this study was to assess the effects of age and sex on the metabolic cost of breathing (V̇o2RM) for exercise ventilations in healthy younger and older males and females. Forty healthy participants (10 young males 24 ± 3 yr; 10 young females 24 ± 3 yr; 10 older males 63 ± 3 yr, 10 older females 63 ± 6 yr) mimicked their exercise breathing patterns (voluntary hyperpnea) in the absence of exercise across a range of exercise intensities. At peak exercise, V̇o2RM represented a significantly greater fraction of peak oxygen consumption (V̇o2peak) in young females, 12.7 ± 4.0%, compared with young males, 10.7 ± 3.0% (P = 0.027), whereas V̇o2RM represented 13.5 ± 2.3% of V̇o2peak in older females and 13.2 ± 3.3% in older males. At relative ventilations, there was a main effect of age, with older males consuming a significantly greater fraction of V̇o2RM (6.6 ± 1.9%) than the younger males (4.4 ± 1.3%; P = 0.012), and older females consuming a significantly greater fraction of V̇o2RM (6.9 ± 2.5%) than the younger females (5.1 ± 1.4%; P = 0.004) at 65% V̇emax. Furthermore, both younger and older males had significantly better respiratory muscle efficiency than their female counterparts at peak exercise (P = 0.011; P = 0.015). Similarly, younger participants were significantly more efficient than older participants (6.5 ± 1.5% vs. 5.5 ± 2.0%; P = 0.001). Normal age-related changes in respiratory function, in addition to sex-based differences in airway anatomy, appear to influence the ventilatory responses and the cost incurred to breathe during exercise.NEW & NOTEWORTHY Here we show that at moderate and high-intensity exercise, older individuals incur a higher cost to breathe than their younger counterparts. However, as individuals age, the sex difference in the cost of breathing narrows. Collectively, our findings suggest that the normative age-related changes in respiratory structure and function, and sex differences in airway anatomy, appear to influence the ventilatory responses to exercise and the oxygen cost to breathe.

No effect of aerobic fitness on exercise-induced diaphragm fatigue in females.

We tested the hypothesis that the incidence and magnitude of diaphragm fatigue following high-intensity exercise would be lower in females with a high aerobic capacity (Hi-Fit) compared with healthy females with an average aerobic fitness (Avg-Fit). Participants were assigned to groups based on their peak O2 uptake (V̇o2peak) obtained during cycle exercise: Hi-Fit n = 9, V̇o2peak ≥ 56.1 ± 3.4 mL·kg-1·min-1 versus Avg-Fit n = 9, V̇o2peak ≤ 35.7 ± 4.9 mL·kg-1·min-1. On the second day, diaphragm fatigue was assessed before and after constant load exercise test to exhaustion. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess diaphragm fatigue by measurement of transdiaphragmatic twitch pressure (Pdi,tw). Both groups exercised at >90% of V̇o2peak for a similar duration (Hi-Fit: 546.1 ± 177.8 vs. Avg-Fit: 559.3 ± 175.0 s, P = 0.9). Diaphragm fatigue was defined as a ≥15% reduction in Pdi,tw, approximately two times greater than the coefficient of variation. The mean group average reduction in Pdi,tw following exercise in the Hi-Fit (17.5%) and Avg-Fit groups (12.2%) was not different between groups (P = 0.2). The Hi-Fit group performed exercise at a higher absolute work rate that elicited significantly greater ventilatory work and inspiratory muscle force output. The Hi-Fit group did not experience greater fatigue compared with the Avg-Fit group, which we attribute to a greater reliance on accessory respiratory muscle recruitment, to training-induced increases in the aerobic capacity of the diaphragm, or a combination of the two. In summary, aerobic fitness is not predictive of exercise-induced diaphragm fatigue in healthy females.NEW & NOTEWORTHY We hypothesized that females with a high aerobic capacity would be resistant to exercise-induced diaphragm fatigue relative to healthy but untrained females. We assessed the pressure generated by the diaphragm following exhaustive exercise by stimulating the phrenic nerves. The magnitude and incidence of fatigue were similar between groups. Despite having higher ventilatory demands during exercise highly trained females were resistant to greater diaphragm fatigue. Aerobic fitness is not predictive of exercise-induced diaphragm fatigue in females.

Sex-based differences in the blood pressure responses to muscle metaboreflex activation are consistent between limb and respiratory muscle.

The purpose of this study was to compare sex-based differences in the mean arterial blood pressure (MAP) response to limb and inspiratory metaboreflex activation, during relative and absolute workloads. Healthy males (n = 9) and females (n = 8) completed pulmonary function testing, forearm volume and circumference measurements, and bouts of limb and inspiratory muscle exercise. The exercises performed included bouts of rhythmic handgrip exercise (RHG) and inspiratory pressure threshold loading (PTL) to task failure, performed in a randomized order and separated by 30 minutes of rest. Participants performed both RHG and PTL at predetermined relative (R) and absolute (A) workloads, while cardiopulmonary measurements were recorded continuously. A time-dependent rise in MAP was observed in all participants, regardless of sex, muscle, or workload (P < 0.001). MAP was greater in males than females during all exercise bouts regardless of muscle group or workload (P < 0.001). The change in MAP from baseline was also greater in males (R-RHG: Δ31 ± 12 mmHg; R-PTL: Δ31 ± 9; A-RHG: Δ35 ± 6; and A-PTL: Δ30 ± 7) than females (R-RHG: Δ21 ± 7 mmHg; R-PTL: Δ13 ± 7; A-RHG: Δ21 ± 7; and A-PTL: Δ14 ± 3) (P < 0.001). Results from this study show that when the forearm and diaphragm perform the same relative or absolute work, the blood pressure response is statistically similar, and both responses are greater in males than females. The findings from the present study suggest that the sex-based difference in the response to metaboreflex activation is similar between the limb and respiratory musculature.NEW & NOTEWORTHY With rhythmic handgrip exercise and inspiratory pressure threshold loading there was a time-dependent rise in the blood pressure that was significantly lower in females than males. The blunted blood pressure response in females was present whether handgrip or inspiratory workload was relative or absolute. An attenuated cardiovascular response to high levels of limb or respiratory muscle work may have implications for whole body exercise in health and disease.

Exercise-induced arterial hypoxemia in female masters athletes.

The purpose of the study was to characterize exercise induced arterial hypoxemia (EIAH) in female masters athletes (FMA). We hypothesized that FMA would experience EIAH during treadmill running. Eight FMA (48-57 years) completed pulmonary function testing and an incremental exercise test until exhaustion (V̇O2max⁡ = 45.7 ± 6.5, range:35-54 ml/kg/min). On a separate day, the participants were instrumented with a radial arterial catheter and an esophageal temperature probe. Participants performed three to four constant load exercise tests at 60-70 %, 75 %, 90 %, 95 %, and 100 % of maximal oxygen uptake while sampling arterial blood and recording esophageal temperature. We found that FMA decrease their partial pressure of oxygen (86.0 ± 7.6, range:73-108 mmHg), arterial saturation (96.2 ± 1.2, range:93-98 %), and widen their alveolar to arterial oxygen difference (23.2 ± 8.8, range:5-42 mmHg) during all exercise intensities however, with variability in terms of severity and pattern. Our findings suggest that FMA experience EIAH however aerobic fitness appears unrelated to occurrence or severity (r = 0.13, p = 0.756).

Perceived exertion and dyspnea while cycling during a hypoxic and hyperoxic placebo.

Rating of perceived exertion (RPE) is used to subjectively quantify the perception of physical activity, breathlessness or dyspnea, and leg discomfort (RPElegs) during exercise. However, it is unknown how dyspnea or RPElegs can be influenced by expectations. Thirty healthy, active participants (19 males, 11 females) completed five, 5-minute submaximal cycling trials at 60% peak work rate. We deceived participants by telling them they were inspiring different hypoxic and hyperoxic gases, when in fact they breathed room air. Cardiorespiratory variables were similar between the trials, however, dyspnea and RPElegs evaluated with a Borg scale changed in a dose-response manner. When participants believed they were breathing 15% O2, they significantly increased dyspnea +0.70 ± 0.2 units (p = 0.03) compared to room air, whereas RPElegs was unchanged +0.35 ± 0.1 units (p = 0.70). When participants believed they were breathing 15% O2, they significantly increased dyspnea +1.05 ± 0.4 units (p = 0.003) compared to 23% hyperoxic condition, whereas RPElegs was unchanged +0.35 ± 0.1 units (p = 0.70). We found that dyspnea during exercise is susceptible to expectancy, without any accompanying physiological changes. Given coaches and clinicians use perceived exertion to prescribe exercise intensity and evaluate treatments, our findings show that the effect of expectations must be considered when interpreting sensations of breathlessness.

Partitioning the work of breathing during running and cycling using optoelectronic plethysmography.

Work of breathing ([Formula: see text]) derived from a single lung volume and pleural pressure is limited and does not fully characterize the mechanical work done by the respiratory musculature. It has long been known that abdominal activation increases with increasing exercise intensity, yet the mechanical work done by these muscles is not reflected in [Formula: see text]. Using optoelectronic plethysmography (OEP), we sought to show first that the volumes obtained from OEP (VCW) were comparable to volumes obtained from flow integration (Vt) during cycling and running, and second, to show that partitioned volume from OEP could be utilized to quantify the mechanical work done by the rib cage ([Formula: see text]RC) and abdomen ([Formula: see text]AB) during exercise. We fit 11 subjects (6 males/5 females) with reflective markers and balloon catheters. Subjects completed an incremental ramp cycling test to exhaustion and a series of submaximal running trials. We found good agreement between VCW versus Vt during cycling (bias = 0.002; P > 0.05) and running (bias = 0.016; P > 0.05). From rest to maximal exercise,[Formula: see text]AB increased by 84% (range: 30%-99%; [Formula: see text]AB: 1 ± 1 J/min to 61 ± 52 J/min). The relative contribution of the abdomen increased from 17 ± 9% at rest to 26 ± 16% during maximal exercise. Our study highlights and provides a quantitative measure of the role of the abdominal muscles during exercise. Incorporating the work done by the abdomen allows for a greater understanding of the mechanical tasks required by the respiratory muscles and could provide further insight into how the respiratory system functions during disease and injury.NEW & NOTEWORTHY We demonstrated that optoelectronic plethysmography (OEP) is a reliable tool to determine ventilatory volume changes during cycling and running, without restricting natural upper arm movements. Second, using OEP volumes coupled with pressure-derived measures, we calculated the work done by the rib cage and abdomen, respectively, during exercise. Collectively, our findings indicate that pulmonary mechanics can be accurately quantified using OEP, and abdominal work performed during ventilation contributes substantially to the overall work of the respiratory musculature.

Respiratory modulation of sympathetic vasomotor outflow during graded leg cycling.

Respiratory modulation of sympathetic vasomotor outflow to skeletal muscles (muscle sympathetic nerve activity; MSNA) occurs in resting humans. Specifically, MSNA is highest at end-expiration and lowest at end-inspiration during quiet, resting breathing. We tested the hypothesis that within-breath modulation of MSNA would be amplified during graded leg cycling. Thirteen (n = 3 females) healthy young (age: 25.2 ± 4.7 yr) individuals completed all testing. MSNA (right median nerve) was measured at rest (baseline) and during semirecumbent cycle exercise at 40%, 60%, and 80% of maximal workload (Wmax). MSNA burst frequency (BF) was 20.0 ± 4.0 bursts/min at baseline and was not different during exercise at 40%Wmax (21.3 ± 3.7 bursts/min; P = 0.292). Thereafter, MSNA BF increased significantly compared with baseline (60%Wmax: 31.6 ± 5.8 bursts/min; P < 0.001, 80%Wmax: 44.7 ± 5.3 bursts/min; P < 0.001). At baseline and all exercise intensities, MSNA BF was lowest at end-inspiration and greatest at mid-to-end expiration. The within-breath change in MSNA BF (ΔMSNA BF; end-expiration minus end-inspiration) gradually increased from baseline to 60%Wmax leg cycling, but no further increase appeared at 80%Wmax exercise. Our results indicate that within-breath modulation of MSNA is amplified from baseline to moderate intensity during dynamic exercise in young healthy individuals, and that no further potentiation occurs at higher exercise intensities. Our findings provide an important extension of our understanding of respiratory influences on sympathetic vasomotor control.NEW & NOTEWORTHY Within-breath modulation of sympathetic vasomotor outflow to skeletal muscle (muscle sympathetic nerve activity; MSNA) occurs in spontaneously breathing humans at rest. It is unknown if respiratory modulation persists during dynamic whole body exercise. We found that MSNA burst frequency was lowest at end-inspiration and highest at mid-to-end expiration during rest and graded leg cycling. Respiratory modulation of sympathetic vasomotor outflow remains intact and is amplified during dynamic whole body exercise.