Sex differences in diaphragmatic fatigue: do young women have an advantage?

Prolonged, high‐intensity aerobic exercise produces muscle fatigue in the diaphragm and accessory respiratory muscles. Respiratory muscle fatigue activates the sympathetically mediated respiratory muscle metaboreflex and results in elevated sympathetic nerve activity (SNA). Elevated SNA augments systemic vasoconstriction and consequently increases mean arterial blood pressure (MAP) and limb vascular resistance. The ultimate consequence of respiratory muscle metaboreflex activation is redistribution of blood from the peripheral circulation (i.e. locomotor muscles) to the fatiguing respiratory muscles, thereby limiting exercise performance.

The use of pressure threshold loading (PTL) allows investigators to examine the cardiovascular consequences of respiratory muscle fatigue without interference from aerobic exercise (i.e. limb muscle activation). While numerous PTL studies have characterized the respiratory muscle metaboreflex in men (Janssens et al. 2013), the appearance and physiological consequences of respiratory muscle fatigue in women have not been fully evaluated. Evidence suggests that women have a blunted respiratory muscle metaboreflex response, potentially due to a female‐specific resistance to inspiratory muscle fatigue. One study (Smith et al. 2016) found that young women exhibited blunted increases in MAP and limb vascular resistance in response to PTL, relative to young men. Thus, whether (1) women possess superior respiratory muscle fatigue resistance to men and (2) if this contributes to a blunted respiratory muscle metaboreflex activation remain to be fully elucidated.

In a recently published article in The Journal of Physiology, Welch et al. (2018) investigated sympathetically mediated cardiovascular responses to PTL in healthy young men and women. Their study sought to (1) uncover sex differences in diaphragmatic fatigue elicited by PTL and (2) compare the cardiovascular responses to inspiratory loading between the sexes. As the female diaphragm is thought to be more fatigue resistant, the authors hypothesized that women would exhibit a blunted cardiovascular excitation in response to PTL relative to male peers.

To test their hypothesis, Welch and colleagues recruited 18 healthy, recreationally active young men (n = 9) and women (n = 9). To control for confounding effects of menstrual phase on cardiovascular function, women were tested in the early follicular phase. Subjects performed one constant‐load PTL trial in which they were required to generate inspiratory pressures at 60% of their maximal inspiratory pressure (calculated from average maximum pressure developed during 5+ Mueller manoeuvres). Breathing frequency (f _b) during the PTL was set to 15 breaths/min with a 0.7 inspiratory duty cycle throughout.

The authors tracked transdiaphragmatic pressures throughout PTL via oesophageal and gastric balloon‐tipped catheters and used cervical magnetic stimulation to evoke maximal diaphragmatic twitches pre‐ and post‐PTL. M‐wave characteristics (captured via surface electromyography) in response to stimulation provided estimates of the stimulator‐driven diaphragm activation and/or pressure development and the change pre‐ and post‐PTL provided an index of diaphragm fatigue (DF). Using this approach, Welch and colleagues showed that men and women exhibited comparable M‐wave characteristics and comparable reductions in transdiaphragmatic twitch pressure pre‐ versus post‐PTL. Thus, the female diaphragm is not protected from PTL‐related fatigue. Remarkably, however, the time to task failure was 10—12 min longer in women than in men, indicative of a slower rate of DF among women.

In regard to cardiovascular indices, beat‐to‐beat changes in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP were monitored throughout the PTL trial. Blood pressure traces were subjected to power‐frequency spectral analysis to identify low‐frequency (∼0.1 Hz) SBP oscillations (LF_SBP) which yielded non‐invasive estimates of efferent sympathetic nerve activity. By task failure, men and women exhibited significantly increased HR, SBP, DBP and MAP relative to baseline. More notably, PTL‐related increases in SBP and MAP were smaller in women than in men, and women also exhibited lower sympathetic activation as estimated by power frequency analyses. Taken together, the results suggest that the magnitude of the respiratory muscle metaboreflex activation seen in women in response to PTL‐induced DF is not as great as that observed in men of the same age.

Whereas the results reported by Welch and colleagues line up nicely with previously published results for either respiratory muscle fatigue (Janssens et al. 2013) or blood pressure regulation (Joyner et al. 2016), theirs is among the initial studies designed to draw a priori comparisons of respiratory muscle fatigue and cardiovascular function in men and women.

The study does have some limitations. LF_SBP, used as a marker of SNA and vasomotor tone, was evaluated during PTL but not at baseline. Therefore, it remains to be determined whether the lower LF_SBP observed during PTL in women reflects an attenuated respiratory muscle metaboreflex, or lower basal SNA. Because young women exhibit lower resting SNA than young men, and changes in SNA are not well correlated with changes in vasomotor tone in young women (Joyner et al. 2016), it may be too soon to draw conclusions about peripheral blood flow based on the present findings.

Although key parameters of the PTL trials, i.e. mean inspiratory load (60% MIP) and inspiratory duty cycle (0.7) are consistent with previously published work (see Jannsens et al. 2013), the breathing rate imposed during PTL was 15 breaths/min. That is, the breathing frequency imposed on subjects more closely resembled the baseline rate for women (14 ± 2 breaths/min) than men (10 ± 2 breaths/min). If all subjects performed at the same relative inspiratory load and same duty cycle, but men were required to increase breathing frequency to a greater extent than women, it seems reasonable that men may have experienced higher respiratory muscle workloads, and in turn, experienced an accelerated rate of DF. While the imposition of a constant breathing rate across all subjects allows for more straightforward analyses and comparison across the sexes, future studies might benefit by matching the breathing frequency imposed during PTL to the individual's natural breathing rate (see, for example, Gross et al. 1979).

In summary, Welch et al. (2018) demonstrate that young women experience delayed DF and attenuated cardiovascular responses to PTL compared to young men. The finding may be attributed to a less vigorous respiratory muscle metaboreflex in women that may impact on their performance during conventional aerobic exercise. The findings also have implications for men and women with compromised exercise tolerance and respiratory muscle function (e.g. heart failure, chronic obstructive pulmonary disease). Thus, future studies could use similar PTL protocols to evaluate how respiratory muscle fatigue and/or aberrant activation of the respiratory muscle metaboreflex may contribute to exercise intolerance among clinical populations.

Additional information

Competing interests

None declared.

Author contributions

Both authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.

Funding

This research was supported by an American Heart Association Postdoctoral Fellowship 18POST33990034 (D.H.C.) and National Institutes of Health Interdisciplinary Training Grant in Cardiovascular Sciences T32 HL007249 (C.M.D.).