Females exhibit greater cardiac volume reductions with expiratory muscle loading during submaximal exercise compared to males

Intrathoracic pressure (ITP) modulates venous return, ventricular filling and ejection throughout the respiratory cycle, and its fluctuations are accentuated during exercise. We sought to determine whether ITP manipulation during submaximal exercise alters cardiac volumes differently in males and females. Young, healthy participants completed two protocols (both n = 30, 15 females): (i) inspiratory loaded breathing (75 W and 30% W_max) and (ii) expiratory loaded breathing (100 W and 60% W_max). We aimed to increase the inspiratory and expiratory load by +20 cmH₂O oesophageal pressure (absolute submaximal trials; 75 and 100 W) and +50% oesophageal pressure swings (relative submaximal trials; 30% and 60% W_max). Intrathoracic pressure was measured with a balloon catheter placed in the oesophagus, and left ventricular volumes and cardiac output were determined via echocardiography. Inspiratory loading increased oesophageal pressure swings relative to spontaneous breathing at both intensities [75 W: +24.2 ± 10.2 cmH₂O (ITP = +77.3%); 30% W_max: +14.3 ± 8.6 cmH₂O (ITP = +53.1%); P < 0.0001] with no difference in stroke volume (SV) [75 W: +3.2 ± 10.1 mL (SV = +3.8%); 30% W_max: +0.7 ± 9.7 mL (SV = +0.8%); P ≥ 0.100] in either sex. Expiratory loading increased oesophageal pressure swings relative to spontaneous breathing [100 W: +23.1 ± 4.1 cmH₂O (ITP = +66.3%); 60% W_max: +17.1 ± 8.5 cmH₂O (ITP = +50.1%); P < 0.0001]. With expiratory loading, SV decreased compared to spontaneous breathing [100 W: -11.4 ± 9.7 mL (SV = -13.8%); 60% W_max: -8.3 ± 9.5 mL (SV = -10.2%); P < 0.0001] with left ventricular end-systolic volume (LVESV) decreasing in females [100 W: -6.5 ± 4.7 mL (LVESV = -13.9%); 60% W_max: -6.1 ± 6.5 mL (LVESV = -13.1%); both P < 0.0006], but not in males [100 W: -1.9 ± 7.2 mL (LVESV = -2.6%); 60% W_max: -0.1 ± 4.8 mL (LVESV = -0.2%); P ≥ 0.409]. Overall, exercise appears to blunt any potential cardiac volume changes with inspiratory loaded breathing, whereas expiratory loaded breathing (less negative ITP) imposes a preload limitation that the exercising heart cannot compensate, thereby unmasking a female-specific reduction in LVESV. KEY POINTS: At rest, more negative intrathoracic pressure (ITP) with inspiratory loading lowers left ventricular end-diastolic volume (LVEDV) and stroke volume (SV). Previous work conducted at maximal exercise shows no cardiac volume changes with inspiratory loading. The mechanisms and any sex-based differences are unknown. During rest and exercise, less negative ITP with expiratory loading reduces LVEDV, SV and cardiac output; however, sex-specific responses remain unclear. Inspiratory loading at submaximal exercise results in no cardiac volume changes and responses were not different between males and females. Expiratory loading at submaximal exercise reduces LVEDV, SV and cardiac output in both sexes; however, females experience greater reductions in cardiac volumes and exhibit a decline in left ventricular end-systolic volume (LVESV). During exercise, potential cardiac volume changes associated with more negative ITP (inspiratory loading) appear to be masked by the cardiovascular responses to exercise, whereas less negative ITP (expiratory loading) imposes an uncompensated preload limitation although females attempt to counter this through LVESV reductions.