The hyperaemic and metaboreflex response of the diaphragm during fatiguing diaphragmatic work in humans

During inspiratory pressure-threshold loading (ITL), the inspiratory muscle metaboreflex (IMM) increases respiratory muscle blood flow, but its effect on diaphragm blood flow (Q̇_di) and fatigue in humans, is unclear. Females exhibit an attenuated IMM compared to males during diaphragmatic loading, suggesting less diaphragm blood flow impedance and metaboreflex activation. We hypothesized that diaphragm hyperaemia would relate positively to metaboreflex sensitivity (i.e. mean arterial pressure change; ΔMAP) and fatigue development (i.e. transdiaphragmatic twitch pressure change; ΔP_di,tw), and be less for females than males. Healthy males and females (11 males and 11 females) completed 6 min of ITL targeting a transdiaphragmatic pressure (P_di) of 80 cmH₂O. Contrast-enhanced ultrasound was used to quantify Q̇_di at baseline, 50% and 100% of task completion. The ΔMAP during loading and the pre- to post-task ΔP_di,tw, via bilateral phrenic nerve electrical stimulation, assessed metaboreflex activation and fatigue, respectively. The accumulated pressure-time-product for P_di (14,177±1,497 cmH₂O·s; mean ± SD) and percentage of maximal P_di (%P_di,max, 51 ± 8%) was not different between sexes (P > 0.600). At 100% of task completion, IMM activation (ΔMAP, +21 mmHg; 95% confidence interval (CI) = 18-24 mmHg; P < 0.0001), diaphragm fatigue (ΔP_di,tw, -18.1 mmHg; 95% CI = -22.2 to -13.9%; P < 0.0001) and hyperaemia (ΔQ̇_di, +15.8 AU s^-1; 95% CI = 12.5-19.1 AU s^-1; P < 0.0001) did not differ between sexes (P ≥ 0.352). There was a significant positive relationship between ΔQ̇_di and %P_di,max (r^2 = 0.211; P = 0.0317), but no relationship between ΔQ̇_di and either ΔMAP (r^2 = 0.011; P = 0.638) or ΔP_di,tw (r^2 = 0.001, P = 0.914). Our data demonstrate that diaphragm hyperaemia relates to relative exercise intensity (%P_di,max) but is not associated with metaboreflex sensitivity, diaphragm fatigue or sex. KEY POINTS: The inspiratory muscle metaboreflex is activated during fatiguing diaphragmatic loading to redistribute blood flow to working muscles. How diaphragm hyperaemia relates to metaboreflex sensitivity or diaphragm fatigue development is unknown. Compared to males, females are reported to have an attenuated inspiratory muscle metaboreflex during both equal absolute and relative intensities, as well as greater diaphragm fatigue resistance during absolute workloads. We investigated whether these sex-based differences result from a lesser hyperaemic response for females compared to males. We found that hyperaemia of the diaphragm was positively correlated with fractional transdiaphragmatic pressure but did not relate to the degree of diaphragm fatigue or metaboreflex sensitivity. Females and males without differences in diaphragmatic strength did not differ in the magnitude of diaphragm hyperaemia, metaboreflex response, or fatigue development.