Inspiratory Pressure-threshold Loading Research Articles

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 y) males (n=9) and females (n=7) completed two experimental days. On day one 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 and 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 (∆ 21±9 mmHg) relative to females (∆ 13±5 mmHg, p=0.026). Males also demonstrated a greater rise in MSNA burst frequency (∆ 18±7 bursts/min) relative to females (∆ 10±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.

Quantifying Diaphragm Blood Flow with Contrast-Enhanced Ultrasound in Humans

Despite the known interplay between blood flow and function, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound (CEUS) to quantify relative diaphragm blood flow (Q̇DIA) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that 1) Q̇DIA would linearly increase with pressure generation, and 2) that there would be good test-retest reliability and inter-analyzer reproducibility. Can we validate the first minimally invasive method to measure relative diaphragm blood flow in humans? Quantitative CEUS of the costal diaphragm was performed in healthy participants (10M/6F; Age 28 ± 5 years; BMI 22.8 ± 2.0 kg·m-2) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured diaphragmatic pressure. Ultrasonography was performed during a constant-rate intravenous infusion of lipid-stabilized microbubbles after each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q̇DIA by two individuals. Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 % of max, respectively. Q̇DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 AU·s-1; P<0.0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day-to-day. Q̇DIA had good-to-excellent test-retest reliability (0.86 [0.77,0.92]; P<0.0001) and excellent inter-analyzer reproducibility (0.93 [0.90,0.95]; P<0.0001) with minimal bias. Relative Q̇DIA measurements have valid physiological underpinnings, are reliable day-to-day, and reproducible analyzer-to-analyzer. Contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q̇DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings.

Respiratory muscle training induces additional stress and training load in well-trained triathletes-randomized controlled trial.

Background: Respiratory muscle training (RMT) has been investigated in the context of improved athletic performance and pulmonary function. However, psychophysiological costs of RMT remain understudied. Voluntary isocapnic hyperpnoea (VIH) and inspiratory pressure threshold loading (IPTL) are widely applied RMT methods. The main purposes of this study were to assess whether RMT induces additional load on well-trained triathletes and determine differences in RMT-induced load between sexes and applied methods. Materials and Methods: 16 well-trained triathletes (n = 16, 56% males) underwent 6weeks of VIH or IPTL program with progressive overload. Blood markers, subjective measures, cardiac indices, near-infrared spectroscopy indices, inspiratory muscle fatigue, and RMT-induced training load were monitored pre-, in and post-sessions. We used multiple ANOVA to investigate effects of sex, training method, and time on measured parameters. Results: There were significant interactions for acid-base balance (p = 0.04 for sex, p < 0.001 for method), partial carbon dioxide pressure (p = 0.03 for sex, p < 0.001 for method), bicarbonate (p = 0.01 for method), lactate (p < 0.001 for method), RMT-induced training load (p = 0.001 for method for single session, p = 0.03 for method per week), average heart rate (p = 0.03 for sex), maximum heart rate (p = 0.02 for sex), intercostales muscle oxygenation (p = 0.007 for testing week), and intercostales muscle oxygenation recovery (p = 0.003 for testing week and p = 0.007 for method). Conclusion: We found that RMT induced additional load in well-trained triathletes. Elicited changes in monitored variables depend on sex and training method. VIH significantly increased subjective training load measures. IPTL was associated with disbalance in blood gasometry, increase in lactate, and reports of headaches and dizziness. Both methods should be applied with consideration in high-performance settings.

Biomarkers to measure respiratory muscle damage following inspiratory pressure threshold loading in healthy young men.

Elevated respiratory muscle work is encountered during strenuous exercise, acute and chronic respiratory disorders, and during inspiratory pressure threshold loading (ITL). ITL can induce respiratory muscle damage, evidenced by increases in fast and slow skeletal troponin-I (sTnI). However, other blood markers of muscle damage have not been measured. We investigated respiratory muscle damage following ITL using a skeletal muscle damage biomarkers panel. Seven healthy men (33 ± 2 yr) undertook 60 min of ITL at a resistance equivalent to ∼0% (Sham ITL) and 70% of their maximal inspiratory pressure 2 wk apart. Serum was collected before and at 1, 24, and 48 h after each ITL session. Creatine kinase muscle-type (CKM), myoglobin, fatty acid-binding protein-3 (FABP3), myosin light chain-3, and fast and slow sTnI were measured. Two-way ANOVA revealed time × load interaction effects (P < 0.05) for CKM, slow and fast sTnI. All of these were higher for 70% compared with Sham ITL. CKM was higher at 1 and 24 h, fast sTnI at 1 h, whereas slow sTnI was higher at 48 h. There were main effects of time (P < 0.01) for FABP3 and myoglobin, but no time × load interaction effects. Hence, CKM and fast sTnI could be used to assess respiratory muscle damage immediately (1 h), whereas CKM and slow sTnI could be used to assess respiratory muscle damage 24 and 48 h following conditions that elevate inspiratory muscle work. The specificity of these markers for different time points needs further exploration in other protocols that cause elevated inspiratory muscle work.NEW & NOTEWORTHY We investigated inspiratory pressure threshold loading-induced respiratory muscle damage using a skeletal muscle damage biomarkers panel. Our investigation showed that creatine kinase muscle-type, and fast skeletal troponin I could be used to assess respiratory muscle damage immediately (1 h), whereas creatine kinase muscle-type, and slow skeletal troponin I could be used to assess respiratory muscle damage 24 and 48 h following conditions that cause elevated inspiratory muscle work.

Potentiated respiratory metaboreflex in older males and females: afferent or efferent mechanisms?

Potentiated respiratory metaboreflex in older males and females: afferent or efferent mechanisms?

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±3years) males (YM; n=10) and females (YF; n=10), as well as older (64±5years) 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±15mmHg, P=0.026); however, there was no difference observed between OF and OM (+26±11 vs. +27±11mmHg, 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±11bpm, P=0.186) or older females and males (+17±7 and +20±7bpm, 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.

Voluntary activation of the diaphragm after inspiratory pressure threshold loading.

After a bout of isolated inspiratory work, such as inspiratory pressure threshold loading (IPTL), the human diaphragm can exhibit a reversible loss in contractile function, as evidenced by a decrease in transdiaphragmatic twitch pressure (PDI,TW ). Whether or not diaphragm fatigability after IPTL is affected by neural mechanisms, measured through voluntary activation of the diaphragm (D-VA) in addition to contractile mechanisms, is unknown. It is also unknown if changes in D-VA are similar between sexes given observed differences in diaphragm fatigability between males and females. We sought to determine whether D-VA decreases after IPTL and whether this was different between sexes. Healthy females (n=11) and males (n=10) completed an IPTL task with an inspired duty cycle of 0.7 and targeting an intensity of 60% maximal transdiaphragmatic pressure until task failure. PDI,TW and D-VA were measured using cervical magnetic stimulation of the phrenic nerves in combination with maximal inspiratory pressure maneuvers. At task failure, PDI,TW decreased to a lesser degree in females vs. males (87 ± 15 vs. 73 ± 12% baseline, respectively, p=0.016). D-VA decreased after IPTL but was not different between females and males (91 ± 8 vs. 88 ± 10% baseline, respectively, p=0.432). When all participants were pooled together, the decrease in PDI,TW correlated with both the total cumulative diaphragm pressure generation (R2 =0.43; p=0.021) and the time to task failure (TTF, R2 = 0.40; p = 0.30) whereas the decrease in D-VA correlated only with TTF (R2 =0.24; p=0.041). Our results suggest that neural mechanisms can contribute to diaphragm fatigability, and this contribution is similar between females and males following IPTL.

Altering magnetic field strength impacts the assessment of diaphragmatic function using cervical magnetic stimulation

Quantifying diaphragm neuromuscular function using cervical magnetic stimulation (CMS) typically uses only a single stimulator (1-Stim) which may be inadequate to maximally stimulate the phrenic nerves. We questioned if using two stimulators (2-Stim) together alters diaphragm neuromuscular function at baseline and following inspiratory pressure threshold loading. Six (n = 3 female) healthy young participants were instrumented with esophageal and gastric balloon tipped catheters and electrodes over the 7–8th intercostal space. With either 1-Stim or 2-Stim an incremental protocol, where the stimulator intensity was progressively increased was completed prior to a series of potentiated twitches. The inspiratory threshold loading test consisted of loaded breathing to failure. Compared to 1-Stim, 2-Stim resulted in significantly greater unpotentiated Pditw and M-waves during the incremental protocol (both p < 0.01). Similarly, 2-Stim resulted in greater potentiated Pditw (31 ± 8 vs. 41 ± 9 cmH2O; p = 0.02) and M-waves (6.4 ± 2.9 vs. 8.6 ± 2.4 V; p = 0.02). Our findings suggest that CMS using 1-Stim is unlikely to generate a sufficient magnetic field to maximally stimulate the phrenic nerves and may underestimate diaphragm function.

Non-invasive assessment of fatigue and recovery of inspiratory rib cage muscles during endurance test in healthy individuals.

Fatigue is defined as loss of capacity to develop muscle force and/or velocity that is reversible at rest. We assessed non-invasively the fatigue and recovery of inspiratory rib cage muscles during two respiratory endurance tests in healthy individuals. The sniff nasal inspiratory pressure (SNIP) was assessed before and after two respiratory endurance tests: normocapnic hyperpnea (NH) and inspiratory pressure threshold loading (IPTL). Contractile (maximum rate of pressure development and time to peak pressure) and relaxation parameters (maximum relaxation rate [MRR], time constant of pressure decay [τ], and half relaxation time) obtained from sniff curves and shortening velocity and mechanical power estimated using optoelectronic plethysmography were analyzed during SNIP maneuvers. Respiratory muscle activity (electromyography) and tissue oxygenation (near-infrared spectroscopy-NIRS) were obtained during endurance tests and SNIP maneuvers. Fatigue development of inspiratory rib cage muscles was assessed according to the slope of decay of median frequency. Peak pressure during SNIP decreased after both protocols (p <0.05). MRR, shortening velocity, and mechanical power decreased (p <0.05), whereas τ increased after IPTL (p <0.05). The median frequency of inspiratory rib cage muscles (i.e., sum of sternocleidomastoid, scalene, and parasternal) decreased linearly during IPTL and exponentially during NH, mainly due to the sternocleidomastoid. Fatigue development behaved differently between protocols and relaxation properties (MRR and τ), shortening velocity, and mechanical power changed only in the IPTL.

Diaphragm Voluntary Activation After Inspiratory Pressure Threshold Loading In Healthy Humans

Inspiratory pressure threshold loading (IPTL) elicits a reduction in diaphragm contractile function (transdiaphragmatic twitch pressure; PDI,TW). It is unknown if diaphragm fatigability after IPTL is also mediated by neural mechanisms (diaphragm voluntary activation; D-VA) or if it differs on the basis of sex. PURPOSE: We sought to determine if D-VA decreases after IPTL and whether this was different between sexes. METHODS: Healthy participants (11F; 10 M) performed IPTL to task failure with an inspired duty cycle of 0.7 at 60% PDI,MAX. Cervical magnetic stimulation of the phrenic nerves was used to assess PDI,TW and D-VA. The relationship between fatigability outcomes (PDI,TW and D-VA), time to task failure, and cumulative diaphragm work were tested to explore how each factor contributes to diaphragm fatigability. RESULTS: Main effects of time (p < 0.001) and sex (p = 0.030), along with an interaction effect (p = 0.007) were observed when examining the changes in PDI,TW after IPTL. Specifically, immediately following IPTL, the decrease in PDI,TW was greater in males compared to females (24 ± 17 vs. 13 ± 15%points; p = 0.016). D-VA was 91 ± 8%baseline in males and 88 ± 11%baseline in females immediately following IPTL. We observed main effects of time, (p < 0.001) but neither the effect of sex (p = 0.177) nor the interaction between sex and time (p = 0.304) were significant, suggesting that D-VA decreases after IPTL similarly in males and females. The decrease in PDI,TW correlated with both the total cumulative diaphragm work (R2 = 0.43; p = 0.021) and time to task failure (R2 = 0.40; p = 0.030), whereas the decrease in D-VA was significantly correlated with time to task failure (R2 = 0.24; p = 0.041) and not cumulative diaphragm work (R2 = 0.19; p = 0.079). CONCLUSION: Our results indicate that neural mechanisms contribute to diaphragm fatigability and this contribution is similar between females and males after IPTL. A decrease in contractile function can be partially explained by both the amount of work performed and the total time of the IPTL task. Decreases in D-VA appear to be influenced primarily by the total time spent performing the IPTL task rather than the amount of work performed. Moreover, these contributing factors appear to be independent of sex. Supported by the Natural Sciences and Engineering Research Council of Canada.

The Respiratory Muscle Metaboreflex: Effects Of Sex And Aging

High levels of respiratory muscle work evoke a sympathetically mediated pressor reflex (e.g. metaboreflex), and young females demonstrate an attenuated heart rate and blood pressure response relative to males. It is unclear what the inter-relationships are between the effects of healthy aging and female sex hormones on the respiratory muscle metaboreflex. PURPOSE: We tested the hypothesis that the pressor response to inspiratory work would be similar between older men and women, and higher relative to their younger counterparts. METHODS: Healthy, normotensive young (26 ± 3 y) males (YM; n = 10) and females (YF; n = 9) and aged (63 ± 6 y) males (OM; n = 5) and females (OF; n = 10, post-menopausal) participated. YF were tested in the mid-luteal phase of the menstrual cycle. Participants performed inspiratory pressure threshold loading (PTL; 60% maximal inspiratory mouth pressure, breathing frequency = 15 bpm, 0.70 inspiratory duty cycle) to task failure. Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously. RESULTS:Time to task failure was different between groups (YF = 19 ± 8. YM = 18 ± 9, OF = 13 ± 6, OM = 8 ± 5 min, p = 0.036). The absolute pressure time product, per minute was also different between groups (p = 0.005); of which, OM generated significantly greater pressures than YW (p = 0.018). There was a significant age (p = 0.002) and sex (p = 0.030) effect in the MAP response to PTL. Peak MAP between OF (+25 ± 10 mmHg) and OM (+17 ± 4 mmHg) were similar (p = 0.999). Peak MAP in OF was greater than YF (+8 ± 6 mmHg, p = 0.010) and was similar to YM (+19 ± 15 mmHg, p = 0.475). The peak MAP response was greater in YM compared to YW (p = 0.009). There was a significant sex, time interaction in the HR response to PTL (p = 0.007). YM showed the greatest peak HR response to PTL (+27 ± 11 bpm) though not significantly different to YF (+15 ± 12 bpm), OF (+17 ± 7 bpm), or OM (+18 ± 6 bpm). CONCLUSIONS:Healthy aging is associated with a heightened respiratory muscle metaboreflex compared to young men and women. The cardiovascular response to the respiratory muscle metaboreflex is similar between older males and post-menopausal females.Support: NSERC

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

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. 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 5min isocapnic PTL tasks targeting a transdiaphragmatic pressure (Pdi ) of 92cmH2 O in normoxia and hypoxia (8% O2 ) were performed on separate days (≥48h). 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±20cmH2 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±1796cmH2 Os-1 , men: 13,717±1231cmH2 Os-1 ; P=0.202) or hypoxia (women: 11,624±1860cmH2 Os-1 , men: 12 722±1502cmH2 Os-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.

The Comparison Effect of Two Pulmonary Rehabilitation Protocols on spirometer indexes and physical performance in patients with COPD.

Background and Objective: Respiratory exercise training based on pulmonary Rehabilitation can lead to improvement of physical function and pulmonary function in COPD patients. The aim of this study was to compare the effects of different protocols of inspiratory pressure threshold loading on some spirometery indexes, physical function and dyspnea in COPD patients. Subjects and Methods: In present semi-experimental research thirty patients with moderate to severe intensity of COPD were selected targetly, and divided randomly in three groups: control (n=10), moderate intensity of inspiratory resistive training (n=10), height intensity of inspiratory resistive training (n=10). Spirometer indexes, dyspnea, and physical function base on 6MWD test were measured before and after pulmonary rehabilitation protocols. Two way ANOVA used for statistical analysis (p 0.05). After pulmonary rehabilitation periods there were no significant differences between FEV1، MVV، FEV1/FVC، VT، 6MWD, and dyspnea levels among control and intervention groups (P>0.05). Conclusion: pulmonary rehabilitation programs based on inspiratory pressure

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

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. 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±5yr, =45.8±9.8mlkg-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±7.5min, 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.

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

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. 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±3years) and women (n=8, age=23±3years) performed PTL whilst targeting a transdiaphragmatic pressure (Pdi ) of 92cmH2 O for 5min. 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±2019cmH2 Os) and women (12,986±1846cmH2 Os; P>0.05); however, women performed the PTL task at a higher relative 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±2.54mmHgmin-1 ) than in women (4.15±2.52mmHgmin-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.

Effect of diaphragm fatigue on subsequent exercise tolerance in healthy men and women.

Women are more resistant to diaphragmatic fatigue (DF) and experience an attenuated inspiratory muscle metaboreflex relative to men. The effects of such sex-based differences on whole body exercise tolerance are yet to be examined. It was hypothesized that DF induced prior to exercise would cause less of a reduction in subsequent exercise time in women compared to men. Healthy men ( n = 9, age = 24 ± 3 yr) and women ( n = 9, age = 24 ± 3 yr) completed a maximal incremental cycle test on day 1. On day 2, subjects performed isocapnic inspiratory pressure-threshold loading (PTL) to task failure followed by a constant load submaximal time-to-exhaustion (TTE) exercise test at 85% of the predetermined peak work rate. On day 3, subjects performed the same exercise test without prior induced DF. Days 2 and 3 were randomized and counterbalanced. Magnetic stimulation of the phrenic nerve roots was used to nonvolitionally assess DF by measurement of transdiaphragmatic twitch pressure ( Pdi,tw). A similar degree of DF was produced in both sexes following PTL [ Pdi,tw (% change from baseline): M = -24.6 ± 7.8%, W = -23.1 ± 5.4%; P = 0.54)]. There was a significant reduction in TTE with prior induced DF compared with the control condition in both men (10.9 ± 3.5 min vs. 13.0 ± 3.2 min, P = 0.05) and women (10.1 ± 2.4 min vs. 12.2 ± 3.3 min, P = 0.03) that did not differ in magnitude between the sexes (M = -15.8 ± 19.5%, W = -14.5 ± 19.2%, P = 0.89). In conclusion, DF negatively and equally impairs exercise tolerance independent of sex. NEW & NOTEWORTHY Women are more resistant to diaphragmatic fatigue (DF) relative to men. The effect of DF on exercise tolerance is currently being debated. Our findings show that DF negatively and equally affects exercise tolerance in healthy men and women. Mechanisms beyond the inspiratory muscle metaboreflex (e.g., dyspnea, central fatigue, breathing pattern) may explain the absence of a sex-based difference.

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

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. 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±3years) and women (n=9, age=24±3years). 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±11vs. 16±11min, respectively; P=0.02). Women exhibited less of an increase in HR (13±8vs. 19±12bpm; P=0.02) and MAP (10±8vs. 14±9mmHg; P=0.01), and significantly lower LFSBP (23±11vs. 34±8mmHg2 ; 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.

Sex Differences in Diaphragmatic Fatigue

Inspiratory muscle fatigue (IMF) is associated with a sympathetically mediated metaboreflex, resulting in time-dependent sympathoexcitation, including increased heart rate, mean arterial pressure and limb vascular resistance that impairs tolerance to exercise. Women may be more resistant to IMF relative to men and therefore, may experience an attenuated inspiratory muscle metaboreflex. PURPOSE: To examine sex-based differences in a) the cardiovascular response to inspiratory pressure-threshold loading (PTL) and b) the effect of prior-induced IMF on subsequent exercise performance. METHODS: Healthy men (n = 9) and women (n = 9) completed a maximal incremental cycle test on day 1. On day 2, subjects performed PTL to task failure followed by a constant load submaximal time-to-exhaustion (TTE) exercise test (85% peak work rate). On day 3, subjects performed the same exercise test without prior-induced IMF. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw) in response to 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, surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. RESULTS: At task failure of PTL, the severity of IMF was similar between sexes (W = 23 ± 6%, M = 24 ± 8% reduction in Pdi,tw, p = 0.33). However, time to task failure was significantly longer in women than men (27 ± 11 vs. 16 ± 11 min, p = 0.02) and consequently, women tended to produce greater cumulative diaphragmatic pressure (46,805 ± 16,723 vs. 32,288 ± 20,752 cmH O⋅s-1; p = 0.06). Furthermore, women exhibited less of an increase in HR (13 ± 8 vs. 19 ± 12 bpm, p = 0.01) and MAP (10 ± 8 vs. 14 ± 9 mmHg, p = 0.02) during PTL, and significantly lower LFSBP (27 ± 12 vs. 38 ± 7 mmHg2, p = 0.04) compared to men. Prior-induced IMF resulted in the premature termination of exercise that did not differ on the basis of sex (W = 15 ± 19%, M = 16 ± 19% decrease in TTE, p = 0.89). CONCLUSIONS: Inspiratory muscle endurance time is significantly longer in women than men. Fatiguing contractions of the diaphragm elicit a blunted cardiovascular response in women, whilst IMF contributes to exercise impairment independent of sex.

Activation of respiratory muscles during respiratory muscle training

It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order.Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax).41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p<0.05). DIA was higher applying IPTL compared to IFRL or VIH (p<0.05).IPTL, IFRL and VIH differ in activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominant in IPTL.

Acute Cardiorespiratory Responses to Inspiratory Pressure Threshold Loading

We tested the acute responses to differing pressure threshold inspiratory loading intensities in well-trained rowers. The purpose of this study was to evaluate 1) how the magnitude of inspiratory pressure threshold loading influences repetition maximum (RM), tidal volume (VT), and external work undertaken by the inspiratory muscle; and 2) whether the inspiratory muscle metaboreflex is activated during acute inspiratory pressure threshold loading. Eight males participated in seven trials. Baseline measurements of maximal inspiratory pressure (PImax), resting tidal volume (VT), and forced vital capacity (FVC) were made. During the remaining sessions, participants undertook a series of resistive inspiratory breathing tasks at loads corresponding to 50%, 60%, 70%, 80%, and 90% of PImax using a pressure threshold inspiratory muscle trainer. The number of repetitions completed at each load, VT, heart rate (fc), and measures of arterial blood pressure was assessed continuously during each trial. A standardized cutoff of 10% FVC was used to define the RM, which decreased as loading intensity increased (P < 0.05). This response was nonlinear, with an abrupt decrease in RM occurring at loads > or =70% of PImax. The most commonly used inspiratory muscle training regimen of 30RM corresponded to 62.5% +/- 4.6% of PImax and also resulted in the highest external work output. Tidal volume (VT) decreased significantly over time at 60%, 70%, and 80% of PImax (P < 0.05), as did the amount of external work completed (P<0.05). Although all loads elicited a sustained increase in fc, only the 60% load elicited a sustained rise in mean arterial blood pressure (P = 0.016), diastolic blood pressure (P = 0.015), and systolic blood pressure (P = 0.002), providing evidence for a metaboreflex response at this load.