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.

The pulmonary physiology of exercise.

The pulmonary system is the first and last "line of defense" in terms of maintaining blood gas homeostasis during exercise. Our review provides the reader with an overview of how the pulmonary system responds to acute exercise. We undertook this endeavor to provide a companion article to "Cardiovascular Response to Exercise," which was published in Advances in Physiological Education. Together, these articles provide the readers with a solid foundation of the cardiopulmonary response to acute exercise in healthy individuals. The intended audience of this review is level undergraduate or graduate students and/or instructors for such classes. By intention, we intend this to be used as an educational resource and seek to provide illustrative examples to reinforce topics as well as highlight uncertainty to encourage the reader to think "beyond the textbook." Our treatment of the topic presents "classic" concepts along with new information on the pulmonary physiology of healthy aging.NEW & NOTEWORTHY Our narrative review is written with the student of the pulmonary physiology of exercise in mind, be it a senior undergraduate or graduate student or those simply refreshing their knowledge. We also aim to provide examples where the reader can incorporate real scenarios.

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.

Acute hypoxia elicits lasting reductions in the sympathetic action potential transduction of arterial blood pressure in males.

Post-hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m2 ) underwent 20 min isocapnic hypoxia (PET O2 : 47 (2) mmHg) and 30 min recovery. Multi-unit microneurography (muscle sympathetic nerve activity; MSNA) and continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 7 min) and late (last 7 min) recovery. AP groups were classified as synchronous APs, asynchronous APs (occurring outside an MSNA burst) and no AP activity. Sympathetic transduction of MAP was quantified using signal-averaging, with ΔMAP tracked following AP group cardiac cycles. Following synchronous APs, ΔMAP was reduced in hypoxia (+1.8 (0.9) mmHg) and early recovery (+1.5 (0.7) mmHg) compared with baseline (+3.1 (2.2) mmHg). AP group-by-condition interactions show that at rest asynchronous APs attenuate MAP reductions compared with no AP activity (-0.4 (1.1) vs. -2.2 (1.2) mmHg, respectively), with no difference between AP groups in hypoxia, early or late recovery. Sympathetic transduction of MAP is blunted in hypoxia and early recovery. At rest, asynchronous sympathetic APs contribute to neural regulation of MAP by attenuating nadir pressure responses. KEY POINTS: Acute isocapnic hypoxia elicits lasting sympathoexcitation that does not correspond to parallel changes in vascular tone, suggesting blunted sympathetic transduction. Signal-averaging techniques track the magnitude and temporal cardiovascular responses following integrated muscle sympathetic nerve activity (MSNA) burst and non-burst cardiac cycles. However, this does not fully characterize the effects of sympathetic action potential (AP) activity on blood pressure control. We show that hypoxia blunts the sympathetic transduction of mean arterial pressure (MAP) following synchronous APs that form integrated MSNA bursts and that sympathetic transduction of MAP remains attenuated into early recovery. At rest, asynchronous APs attenuate the reduction in MAP compared with cardiac cycles following no AP activity, thus asynchronous sympathetic APs appear to contribute to the neural regulation of blood pressure. The results advance our understanding of sympathetic transduction of arterial pressure during and following exposure to acute isocapnic hypoxia in humans.

Sex differences in diaphragmatic fatigue: Effects of hypoxia during inspiratory loading.

KEY POINTS: Under normoxic conditions, both healthy female and male diaphragms fatigue at a similar degree when matched for absolute diaphragmatic work during inspiratory loading. We investigated whether similarities in diaphragm fatigability persist under acute hypoxic conditions. We found that, in acute hypoxia, fatigue of the diaphragm is greater in women compared to men, whereas the magnitude of fatigue in normoxia did not differ between sexes. When matched for maximal diaphragm strength, women and men had a similar pressor response to work-matched inspiratory loading, independent of oxygen availability. ABSTRACT: In normoxia, women and men display a comparable magnitude of diaphragmatic fatigue (DF) after work-matched inspiratory loading. Whether these sex similarities are maintained under acute hypoxic conditions is unknown. We investigated the influence of acute hypoxia during work-matched inspiratory pressure-threshold loading (PTL) on DF in healthy women (n = 8) and men (n = 8). Two 5 min isocapnic PTL tasks targeting a transdiaphragmatic pressure (Pdi ) of 92 cmH2 O in normoxia and hypoxia (8% O2 ) were performed on separate days (≥48 h). DF was quantified by twitch Pdi (Pdi,tw ) via cervical magnetic stimulation post-PTL. Women and men had similar maximal Pdi (Pdi,max ; women: 171 ± 16, men: 178 ± 20 cmH2 O) and relative target workload (women: 54 ± 5%, men: 53 ± 6% Pdi,max ). The absolute cumulative diaphragmatic work did not differ between sexes in normoxia (women: 12,653 ± 1796 cmH2 O s-1 , men: 13,717 ± 1231 cmH2 O s-1 ; P = 0.202) or hypoxia (women: 11,624 ± 1860 cmH2 O s-1 , men: 12 722 ± 1502 cmH2 O s-1 ; P = 0.189). In normoxia, the magnitude of reduction in Pdi,tw post-PTL was similar between sexes (women: -21.1 ± 8.4%, men: -22.5 ± 4.9 %; P = 0.193); however, a higher degree of DF was observed in women compared to men following PTL in acute hypoxia (women: -27.6 ± 7.7%, men: -23.4 ± 9.6%, P = 0.019). We conclude that the female diaphragm is more susceptible to fatigue after inspiratory loading under acute hypoxic conditions. This finding may be related to sex differences in diaphragm muscle metabolism, such as fibre type composition, contractile properties, substrate utilisation and blood perfusion.

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.

The effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography during exercise in healthy males.

KEY POINTS: Diaphragm fatigue may increase the intensity (sensory dimension) and unpleasantness (affective dimension) of dyspnoea, which may partially explain why diaphragm fatigue negatively affects exercise performance. We hypothesized that diaphragm fatigue would negatively affect exercise performance via increases in both the intensity and unpleasantness of dyspnoea, and that the increase in dyspnoea would be mechanistically linked to an increase in diaphragmatic EMG (EMGdi ), a surrogate measure of neural respiratory drive. Fatiguing the diaphragm prior to exercise reduced cycling performance and increased both the intensity and unpleasantness of dyspnoea. The change in submaximal dyspnoea unpleasantness was significantly correlated with the change in cycling performance. Pre-fatigue of the diaphragm did not increase EMGdi during exercise and is therefore unrelated to the increase in either the sensory or affective dimension of exertional dyspnoea. ABSTRACT: The purpose of this study was to examine the effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography (EMGdi ) during cycling. Sixteen healthy males (age = 27 ± 5 yr, V̇O2max  = 45.8 ± 9.8 ml kg-1  min-1 ) completed two high-intensity, time-to-exhaustion cycling tests in randomized order: (i) inspiratory pressure threshold loading (PTL) prior to exercise to induce diaphragm fatigue (pre-DF) and (ii) no PTL (control). Diaphragm fatigue after PTL was confirmed via cervical magnetic stimulation of the phrenic nerves. Dyspnoea intensity and unpleasantness were measured throughout exercise with the 0-10 category-ratio Borg scale and following exercise using the Multidimensional Dyspnoea Profile (MDP). EMGdi was continuously recorded via a multipair oesophageal electrode catheter. Time-to-exhaustion decreased with pre-DF vs. control (9.0 ± 5.5 vs. 10.7 ± 7.5 min, P = 0.023). Pre-DF increased dyspnoea intensity ratings by 0.6 ± 1.0 Borg 0-10 units at the highest equivalent submaximal exercise time (HESET) a participant could achieve in both conditions (P = 0.020). Dyspnoea unpleasantness ratings increased with pre-DF by 0.5 ± 1.0, 0.7 ± 1.2 and 0.9 ± 1.4 (all P < 0.05) Borg 0-10 units during the 2nd, 3rd and 4th minutes of exercise, respectively. There was a significant correlation between the change in breathing unpleasantness ratings at HESET and the change in time-to-exhaustion (r = 0.66, P = 0.006). The immediate perception domain, a combination of peak unpleasantness and specific dyspnoea descriptor intensity ratings, was the only component of the MDP that was significantly increased with pre-DF (4.3 ± 1.9 vs. 3.6 ± 1.8, P = 0.04). There were no significant differences in EMGdi . In conclusion, diaphragm fatigue has negative effects on multiple domains of dyspnoea, which may partially explain why exercise performance decreases with it.

The hyperpnoea of exercise in health: Respiratory influences on neurovascular control.

NEW FINDINGS: What is the topic of this review? Elevated demand is placed on the respiratory muscles during whole-body exercise-induced hyperpnoea. What is the role of elevated demand in neural modulation of cardiovascular control in respiratory and locomotor skeletal muscle, and what are the mechanisms involved? What advances does it highlight? There is a sympathetic restraint of blood flow to locomotor muscles during near-maximal exercise, which might function to maintain blood pressure. During submaximal exercise, respiratory muscle blood flow might be also be reduced if ventilatory load is sufficiently high. Methodological advances (near-infrared spectroscopy with indocyanine green) confirm that blood flow is diverted away from respiratory muscles when the work of breathing is alleviated. ABSTRACT: It is known that the respiratory muscles have a significant increasing oxygen demand in line with hyperpnoea during whole-body endurance exercise and are susceptible to fatigue, in much the same way as locomotor muscles. The act of ventilation can itself be considered a form of exercise. The manipulation of respiratory load at near-maximal exercise alters leg blood flow significantly, demonstrating a competitive relationship between different skeletal muscle vascular beds to perfuse both sets of muscles adequately with a finite cardiac output. In recent years, the question has moved towards whether this effect exists during submaximal exercise, and the use of more direct measurements of respiratory muscle blood flow itself to confirm assumptions that uphold the concept. Evidence thus far has shown that there is a reciprocal effect on blood flow redistribution during ventilatory load manipulation observed at the respiratory muscles themselves and that the effect is observable during submaximal exercise, where active limb blood flow was reduced in conditions that simulated a high work of breathing. This has clinical applications for populations with respiratory disease and heart failure, where the work of breathing is remarkably high, even during submaximal efforts.

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.

Quantifying the mechanical work of breathing in men and women during rowing.

PURPOSE: To quantify the mechanical work of breathing (Wb) during an indoor rowing test in men and women. Additionally, to compare sex-based differences in the Wb and its components through a rowing test. METHODS: Fifteen collegiate rowers were recruited (8 women/7 men) and performed a 2000 m rowing test on a rowing ergometer. Esophageal pressure was measured during exercise via balloon catheterization, after which pressure-volume curves were used to calculate total, inspiratory resistive and elastic, and total expiratory Wb. RESULTS: Men had significantly higher values of instantaneous and cumulative total Wb at and beyond 37.5% (430.4 ± 42.5 vs. 282.1 ± 45.1 J min-1, P < 0.05) and 62.5% (1946.8 ± 150.9 vs. 1360.1 ± 197.2 J, P < 0.05) total exercise time, respectively. However, when compared at the same minute ventilation, women had higher values of total (at and above ~ 140 L min-1), inspiratory resistive (at and above ~ 120 L min-1), and inspiratory elastic (at and above ~ 135 L min-1) Wb, whereas men presented higher total expiratory Wb compared to women at any ventilation. CONCLUSION: Although female rowers present higher relative values of inspiratory resistive and elastic Wb, their male counterparts develop greater ventilatory efforts during a 2000 m rowing test, resulting in a larger total mechanical Wb. We interpret these findings to mean that the Wb reflects both anatomical (i.e., airways and lung sizes) and respiratory (i.e., minute ventilation) sex differences during rowing.

Cardiopulmonary Demand of 16-kg Kettlebell Snatches in Simulated Girevoy Sport.

Chan, M, MacInnis, MJ, Koch, S, MacLeod, KE, Lohse, KR, Gallo, ME, Sheel, AW, and Koehle, MS. Cardiopulmonary demand of 16-kg kettlebell snatches in simulated Girevoy Sport. J Strength Cond Res 34(6): 1625-1633, 2020-Kettlebell lifting has become popular both as a strength and conditioning training tool and as a sport in and of itself: Girevoy Sport (GS). Although several kettlebell multimovement protocols have been analyzed, little research has attempted to quantify the aerobic stimulus of the individual events in GS, which could better inform kettlebell-related exercise prescription. The purpose of this study was to quantify the cardiopulmonary demand, assessed primarily by oxygen consumption (V[Combining Dot Above]O2) and heart rate (HR), of continuous high-intensity kettlebell snatches-under conditions relevant to GS-and to compare this demand with a more traditional graded rowing ergometer maximal exercise test. Ten male participants (age = 28.4 ± 4.6 years, height = 185 ± 7 cm, body mass = 95.1 ± 14.9 kg) completed (a) a graded-exercise test on a rowing ergometer to determine maximal oxygen consumption (V[Combining Dot Above]O2max) and maximal heart rate (HRmax) and (b) a graded-exercise test consisting of continuous 16-kg kettlebell snatches to determine peak oxygen consumption (V[Combining Dot Above]O2peak) and peak heart rate (HRpeak) during a simulated GS snatch event. Subjects achieved a V[Combining Dot Above]O2max of 45.7 ± 6.7 ml·kg·min and HRmax of 177 ± 8.3 b·min on the rowing ergometer. The kettlebell snatch test produced a V[Combining Dot Above]O2peak of 37.6 ± 4.4 ml·kg·min (82.7 ± 6.5% V[Combining Dot Above]O2max) and a HRpeak of 174 ± 10 b·min (98.0 ± 3.4% HRmax). These findings suggest that GS kettlebell snatches with 16-kg can provide an adequate aerobic stimulus to improve cardiorespiratory fitness in those with a V[Combining Dot Above]O2max of ≤51 ml·kg·min, according to aerobic training recommendations from the American College of Sports Medicine.

Respiratory muscle training in athletes with cervical spinal cord injury: effects on cardiopulmonary function and exercise capacity.

KEY POINTS: The effect of combined inspiratory and expiratory muscle training on resting and reflexive cardiac function, as well as exercise capacity, in individuals with cervical spinal cord injury (SCI) is presently unknown. Six weeks of combined inspiratory and expiratory muscle training enhances both inspiratory and expiratory muscle strength in highly-trained athletes with cervical SCI with no significant effect on lung function. There was a significant decrease in left-ventricular filling and stroke volume at rest in response to 45° head-up tilt, which is irreversible by respiratory muscle training. Combined inspiratory and expiratory muscle training increased peak aerobic work rate and reduced end-expiratory lung volumes during exercise, which may have implications for left-ventricular filling during exercise. ABSTRACT: To investigate the pulmonary, cardiovascular and exercise responses to combined inspiratory and expiratory respiratory muscle training (RMT) in athletes with tetraplegia, six wheelchair rugby athletes (five males and one female, aged 33 ± 5 years) completed 6 weeks of pressure threshold RMT, 2 sessions day-1 on 5 days week-1 . Resting pulmonary and cardiac function, exercise capacity, exercising lung volumes and field-based exercise performance were assessed at pre-RMT, post-RMT and after a 6-week no RMT period. RMT enhanced maximal inspiratory (pre- vs. post-RMT: -76 ± 15 to -106 ± 23 cmH2 O, P = 0.002) and expiratory (59 ± 26 to 73 ± 32 cmH2 O, P = 0.007) mouth pressures, as well as peak expiratory flow (6.74 ± 1.51 vs. 7.32 ± 1.60 L/s, P < 0.04). Compared to pre-RMT, peak work rate was higher at post-RMT (60 ± 23 to 68 ± 22 W, P = 0.003), whereas exercising end-expiratory lung volumes were reduced (P < 0.017). Peak oxygen uptake increased in all athletes at post-RMT (1.24 ± 0.40 vs. 1.40 ± 0.50 l min-1 , P = 0.12). After 6 weeks of no RMT all indices returned towards baseline, with peak work rate (P = 0.037), peak oxygen uptake (P = 0.041) and end-expiratory lung volume (P < 0.034) being significantly lower at follow-up than at post-RMT. There was a significant decrease in left-ventricular end-diastolic volume and stroke volume in response to 45° head-up tilt (P = 0.030 and 0.021, respectively); however, all cardiac indices in both supine and tilted positions were unchanged by RMT. Our findings demonstrate the efficacy of RMT with respect to enhancing respiratory muscle strength, lowering exercising lung volumes and increasing exercise capacity. Although the precise mechanisms by which RMT may enhance exercise capacity remain unclear, our data suggest that it is probably not the result of a direct cardiac adaptation associated with RMT.

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.

Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

KEY POINTS: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. ABSTRACT: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.

Analysis of maximal expiratory flow-volume curves in adult survivors of preterm birth.

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE (n = 19), BPD (n = 25), and CON (n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD (P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20-30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

Modelling the effects of age and sex on the resistive and viscoelastic components of the work of breathing during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of age and sex on the resistive and viscoelastic components of work of breathing (Wb ) during exercise? What is the main finding and its importance? The resistive and viscoelastic components of Wb were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of Wb was higher in females than in males, regardless of age. These findings contribute to improving our understanding of the effects of ageing and sex on the mechanical ventilatory response to exercise. ABSTRACT: Healthy ageing and biological sex each affect the work of breathing (Wb ) for a given minute ventilation ( V̇E ). Age-related structural changes to the respiratory system lead to an increase in both the resistive and viscoelastic components of Wb ; however, it is unclear whether healthy ageing differentially alters the mechanics of breathing in males and females. We analysed data from 22 older (60-80 years, n = 12 females) and 22 younger (20-30 years, n = 11 females) males and females that underwent an incremental cycle exercise test to exhaustion. V̇E and Wb were assessed at rest and throughout exercise. Wb - V̇E data for each participant were fitted to a non-linear equation (i.e. Wb  = a V̇E3 + b V̇E2 ) that partitions Wb into resistive (i.e. a V̇E3 ) and viscoelastic (i.e. b V̇E2 ) components. We then modelled the effects of healthy ageing and biological sex on each component of Wb . Overall, the model fit was excellent (r2 : 0.99 ± 0.01). There was a significant main effect of age and sex on the resistive component of Wb (both P < 0.05), and a significant main effect of age (P < 0.001), but not sex (P = 0.309), on the viscoelastic component of Wb . No significant interactions between age and sex on a V̇E3 or b V̇E2 were noted (both P > 0.05). Our findings indicate that during exercise: (i) the higher total Wb in females relative to males is due to a higher resistive, but not viscoelastic, component of Wb , and (ii) regardless of sex, the higher Wb in older adults relative to younger adults is due to higher resistive and viscoelastic components of Wb .

Effect of increased inspiratory muscle work on blood flow to inactive and active limbs during submaximal dynamic exercise.

NEW FINDINGS: What is the central question of this study? Increased respiratory muscle activation is associated with neural and cardiovascular consequences via the respiratory muscle metaboreflex. Does increased sympathetic vasoconstriction originating from the respiratory musculature elicit a reduction in blood flow to an inactive limb in order to maintain blood flow to an active limb? What is the main finding and its importance? Arm blood flow was reduced whereas leg blood flow was preserved during mild leg exercise with inspiratory resistance. Blood flow to the active limb is maintained via sympathetic control of blood flow redistribution when the respiratory muscle-induced metaboreflex is activated. ABSTRACT: The purpose of this study was to elucidate the effect of increasing inspiratory muscle work on blood flow to inactive and active limbs. Healthy young men (n = 10, 20 ± 2 years of age) performed two bilateral dynamic knee-extension and knee-flexion exercise tests at 40% peak oxygen uptake for 10 min. The trials consisted of spontaneous breathing for 5 min followed by voluntary hyperventilation either with or without inspiratory resistance for 5 min (40% of maximal inspiratory mouth pressure, inspiratory duty cycle of 50% and a breathing frequency of 40 breaths min-1 ). Mean arterial blood pressure was acquired using finger photoplethysmography. Blood flow in the brachial artery (inactive limb) and in the femoral artery (active limb) were monitored using Doppler ultrasound. Mean arterial blood pressure during exercise was higher (P < 0.05) with inspiratory resistance (121 ± 7 mmHg) than without resistance (99 ± 5 mmHg). Brachial artery blood flow increased during exercise without inspiratory resistance (120 ± 31 ml min-1 ) compared with the resting level, whereas it was attenuated with inspiratory resistance (65 ± 43 ml min-1 ). Femoral artery blood flow increased at the onset of exercise and was maintained throughout exercise without inspiratory resistance (2576 ± 640 ml min-1 ) and was unchanged when inspiratory resistance was added (2634 ± 659 ml min-1 ; P > 0.05). These results suggest that sympathetic control of blood redistribution to active limbs is facilitated, in part, by the respiratory muscle-induced metaboreflex.

Sex Differences in the Pulmonary System Influence the Integrative Response to Exercise.

Healthy women have proportionally smaller lungs and airways compared with height-matched men. These anatomical sex-based differences result in greater mechanical ventilatory constraints and may influence the integrative response to exercise. Our review will examine this hypothesis in healthy humans in the context of dynamic whole-body exercise.

Sex differences in diaphragmatic fatigue: the cardiovascular response to inspiratory resistance.

KEY POINTS: Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance. Women may be more resistant to DF compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure-threshold loading (PTL) performed to task failure. At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men. For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men. Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance. ABSTRACT: Diaphragmatic fatigue (DF) elicits reflexive increases in sympathetic vasomotor outflow (i.e. metaboreflex). There is some evidence suggesting women may be more resistant to DF compared to men, and therefore may experience an attenuated inspiratory muscle metaboreflex. To this end, we sought to examine the cardiovascular response to inspiratory resistance in healthy young men (n = 9, age = 24 ± 3 years) and women (n = 9, age = 24 ± 3 years). Subjects performed isocapnic inspiratory pressure-threshold loading (PTL, 60% maximal inspiratory mouth pressure) to task failure. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw ) using cervical magnetic stimulation. Heart rate (HR) and mean arterial pressure (MAP) were measured beat-by-beat throughout PTL via photoplethysmography, and low-frequency systolic pressure (LFSBP ; a surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. At PTL task failure, the degree of DF was similar between sexes (∼23% reduction in Pdi,tw ; P = 0.33). However, time to task failure was significantly longer in women than in men (27 ± 11 vs. 16 ± 11 min, respectively; P = 0.02). Women exhibited less of an increase in HR (13 ± 8 vs. 19 ± 12 bpm; P = 0.02) and MAP (10 ± 8 vs. 14 ± 9 mmHg; P = 0.01), and significantly lower LFSBP (23 ± 11 vs. 34 ± 8 mmHg2 ; P = 0.04) during PTL compared to men. An attenuation of the inspiratory muscle metaboreflex may influence limb and respiratory muscle haemodynamics with implications for exercise performance.

Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease.

Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung disease (ILD) is incomplete. The aims of this study were two-fold: 1) to determine whether dyspnoea intensity is better predicted by neural respiratory drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1 comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted of constant-load cycling while breathing room air or 60% oxygen to address Aim 2. Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was calculated as the ratio between EMGdi (%max) and tidal volume (%vital capacity).On adjusted analysis, NMU and its constituents were all significantly associated with dyspnoea ratings during incremental cycling, with EMGdi having the strongest correlation. The between-treatment change in dyspnoea ratings during constant load cycling was only correlated with change in exercise endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was better predicted by improvements in NMU.