{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:08:13Z","timestamp":1788433693567,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102020\u201004010"],"award-info":[{"award-number":["RGPIN\u20102020\u201004010"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015752","name":"British Columbia Lung Association","doi-asserted-by":"publisher","award":["AWD\u2010027450"],"award-info":[{"award-number":["AWD\u2010027450"]}],"id":[{"id":"10.13039\/100015752","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>During inspiratory pressure\u2010threshold loading (ITL), the inspiratory muscle metaboreflex (IMM) increases respiratory muscle blood flow, but its effect on diaphragm blood flow (Q\u0307<jats:sub>di<\/jats:sub>) 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; \u0394MAP) and fatigue development (i.e. transdiaphragmatic twitch pressure change; \u0394P<jats:sub>di,tw<\/jats:sub>), and be less for females than males. Healthy males and females (11 males and 11 females) completed 6\u00a0min of ITL targeting a transdiaphragmatic pressure (P<jats:sub>di<\/jats:sub>) of 80\u00a0cmH<jats:sub>2<\/jats:sub>O. Contrast\u2010enhanced ultrasound was used to quantify Q\u0307<jats:sub>di<\/jats:sub> at baseline, 50% and 100% of task completion. The \u0394MAP during loading and the pre\u2010 to post\u2010task \u0394P<jats:sub>di,tw<\/jats:sub>, via bilateral phrenic nerve electrical stimulation, assessed metaboreflex activation and fatigue, respectively. The accumulated pressure\u2010time\u2010product for P<jats:sub>di<\/jats:sub> (14,177\u00b11,497\u00a0cmH<jats:sub>2<\/jats:sub>O\u00b7s; mean\u00a0\u00b1\u00a0SD) and percentage of maximal P<jats:sub>di<\/jats:sub> (%P<jats:sub>di,max<\/jats:sub>, 51\u00a0\u00b1\u00a08%) was not different between sexes (<jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.600). At 100% of task completion, IMM activation (\u0394MAP, +21\u00a0mmHg; 95% confidence interval\u00a0(CI)\u00a0=\u00a018\u201324\u00a0mmHg; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001), diaphragm fatigue (\u0394P<jats:sub>di,tw<\/jats:sub>, \u221218.1\u00a0mmHg; 95% CI\u00a0=\u00a0\u221222.2 to \u221213.9%; <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.0001) and hyperaemia (\u0394Q\u0307<jats:sub>di<\/jats:sub>, +15.8\u00a0AU\u00a0s<jats:sup>\u22121<\/jats:sup>; 95% CI\u00a0=\u00a012.5\u201319.1\u00a0AU\u00a0s<jats:sup>\u22121<\/jats:sup>; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) did not differ between sexes (<jats:italic>P<\/jats:italic>\u00a0\u2265\u00a00.352). There was a significant positive relationship between \u0394Q\u0307<jats:sub>di<\/jats:sub> and %P<jats:sub>di,max<\/jats:sub> (<jats:italic>r<\/jats:italic><jats:sup>2\u00a0=\u00a0<\/jats:sup>0.211; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0317), but no relationship between \u0394Q\u0307<jats:sub>di<\/jats:sub> and either \u0394MAP (<jats:italic>r<\/jats:italic><jats:sup>2\u00a0=\u00a0<\/jats:sup>0.011; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.638) or \u0394P<jats:sub>di,tw<\/jats:sub> (<jats:italic>r<\/jats:italic><jats:sup>2\u00a0=\u00a0<\/jats:sup>0.001, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.914). Our data demonstrate that diaphragm hyperaemia relates to relative exercise intensity (%P<jats:sub>di,max<\/jats:sub>) but is not associated with metaboreflex sensitivity, diaphragm fatigue or sex.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70040-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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\u2010based differences result from a lesser hyperaemic response for females compared to males.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Females and males without differences in diaphragmatic strength did not differ in the magnitude of diaphragm hyperaemia, metaboreflex response, or fatigue development.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288837","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T14:55:14Z","timestamp":1755615314000},"page":"5805-5825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The hyperaemic and metaboreflex response of the diaphragm during fatiguing diaphragmatic work in humans"],"prefix":"10.1113","volume":"603","author":[{"given":"Megan L.","family":"Lance","sequence":"first","affiliation":[{"name":"Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences University of British Columbia  Kelowna BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-8430","authenticated-orcid":false,"given":"Christina D.","family":"Bruce","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences University of British Columbia  Kelowna BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison M.","family":"Coyle","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences University of British Columbia  Kelowna BC 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