["The Journal of Physiology, Volume 604, Issue 7, Page 3175-3200, 1 April 2026. ", "\nAbstract figure legend Intrathoracic pressure (ITP) manipulation during submaximal exercise reveals load‐ and sex‐specific cardiac volume responses. Inspiratory loading increased oesophageal pressure swings and the work of breathing (Wb) but did not alter stroke volume (SV) or ventricular volumes in males or females. Expiratory loading increased oesophageal pressure swings and the Wb which led to reductions in SV in both sexes. Females exhibited greater reductions in cardiac volumes, characterized by a distinctive decrease in left ventricular end‐systolic volume (LVESV) not observed in males. The findings suggest that during exercise, inspiratory loading effects are masked by normal cardiovascular adjustments, whereas expiratory loading imposes a preload constraint that unmasked female‐specific limitations in ventricular filling and ejection. Abbreviations: LVEDV, left ventricular end‐diastolic volume; Peso, oesophageal pressure.\n\n\n\n\n\n\n\n\n\nAbstract\nIntrathoracic 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% Wmax) and (ii) expiratory loaded breathing (100 W and 60% Wmax). 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% Wmax). 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% Wmax: +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% Wmax: +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% Wmax: +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% Wmax: −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% Wmax: −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% Wmax: −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.\n\n\n\n\n\n\n\n\n\nKey points\n\nAt 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.\nDuring rest and exercise, less negative ITP with expiratory loading reduces LVEDV, SV and cardiac output; however, sex‐specific responses remain unclear.\nInspiratory loading at submaximal exercise results in no cardiac volume changes and responses were not different between males and females.\nExpiratory 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).\nDuring 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.\n\n\n"]