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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                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a030, 15 females): (i) inspiratory loaded breathing (75\u00a0W and 30%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) and (ii) expiratory loaded breathing (100\u00a0W and 60%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ). We aimed to increase the inspiratory and expiratory load by +20\u00a0cmH\n                      <jats:sub>2<\/jats:sub>\n                      O oesophageal pressure (absolute submaximal trials; 75 and 100\u00a0W) and +50% oesophageal pressure swings (relative submaximal trials; 30% and 60%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ). 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\u00a0W: +24.2\u00a0\u00b1\u00a010.2\u00a0cmH\n                      <jats:sub>2<\/jats:sub>\n                      O (ITP\u00a0=\u00a0+77.3%); 30% W\n                      <jats:sub>max<\/jats:sub>\n                      : +14.3\u00a0\u00b1\u00a08.6\u00a0cmH\n                      <jats:sub>2<\/jats:sub>\n                      O (ITP\u00a0=\u00a0+53.1%);\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001] with no difference in stroke volume (SV) [75\u00a0W: +3.2\u00a0\u00b1\u00a010.1\u00a0mL (SV\u00a0=\u00a0+3.8%); 30%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      : +0.7\u00a0\u00b1\u00a09.7\u00a0mL (SV\u00a0=\u00a0+0.8%);\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2265\u00a00.100] in either sex. Expiratory loading increased oesophageal pressure swings relative to spontaneous breathing [100\u00a0W: +23.1\u00a0\u00b1\u00a04.1\u00a0cmH\n                      <jats:sub>2<\/jats:sub>\n                      O (ITP\u00a0=\u00a0+66.3%); 60%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      : +17.1\u00a0\u00b1\u00a08.5\u00a0cmH\n                      <jats:sub>2<\/jats:sub>\n                      O (ITP\u00a0=\u00a0+50.1%);\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001]. With expiratory loading, SV decreased compared to spontaneous breathing [100\u00a0W: \u221211.4\u00a0\u00b1\u00a09.7\u00a0mL (SV\u00a0=\u00a0\u221213.8%); 60%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      : \u22128.3\u00a0\u00b1\u00a09.5\u00a0mL (SV\u00a0=\u00a0\u221210.2%);\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001] with left ventricular end\u2010systolic volume (LVESV) decreasing in females [100\u00a0W: \u22126.5\u00a0\u00b1\u00a04.7\u00a0mL (LVESV\u00a0=\u00a0\u221213.9%); 60%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      : \u22126.1\u00a0\u00b1\u00a06.5\u00a0mL (LVESV\u00a0=\u00a0\u221213.1%); both\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0006], but not in males [100\u00a0W: \u22121.9\u00a0\u00b1\u00a07.2\u00a0mL (LVESV\u00a0=\u00a0\u22122.6%); 60%\n                      <jats:italic>W<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      : \u22120.1\u00a0\u00b1\u00a04.8\u00a0mL (LVESV\u00a0=\u00a0\u22120.2%);\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0\u2265\u00a00.409]. 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\u2010specific reduction in LVESV.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70405-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>At rest, more negative intrathoracic pressure (ITP) with inspiratory loading lowers left ventricular end\u2010diastolic 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\u2010based differences are unknown.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>During rest and exercise, less negative ITP with expiratory loading reduces LVEDV, SV and cardiac output; however, sex\u2010specific responses remain unclear.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Inspiratory loading at submaximal exercise results in no cardiac volume changes and responses were not different between males and females.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>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\u2010systolic volume (LVESV).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>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.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290476","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:28:50Z","timestamp":1773001730000},"page":"3175-3200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Females exhibit greater cardiac volume reductions with expiratory muscle loading 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