{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:03:28Z","timestamp":1789506208399,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2022\u201003641"],"award-info":[{"award-number":["2022\u201003641"]}],"id":[{"id":"10.13039\/501100000038","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":[[2026,9]]},"abstract":"\n Abstract<\/jats:title>\n \n Central blood volume (CBV) is a key haemodynamic determinant of pulmonary diffusing capacity for carbon monoxide (DL\n CO<\/jats:sub>\n ) and its components, capillary blood volume (\n V<\/jats:italic>\n c<\/jats:sub>\n ) and membrane diffusing capacity (\n D<\/jats:italic>\n m,CO<\/jats:sub>\n ). However the contribution of CBV to DL\n CO<\/jats:sub>\n regulation remains poorly defined. We tested the hypothesis that graded increases and decreases in CBV would elicit differential changes in DL\n CO<\/jats:sub>\n , primarily driven by\n V<\/jats:italic>\n c<\/jats:sub>\n . Eighteen healthy young adults (6 women; age: 25 [3] years; : 44.5 [8.5] mL\/kg\/min) completed supine graded lower body positive (LBPP) and negative pressure (LBNP). DL\n CO<\/jats:sub>\n ,\n V<\/jats:italic>\n c<\/jats:sub>\n and\n D<\/jats:italic>\n m,CO<\/jats:sub>\n were assessed using the combined DL\n CO,NO<\/jats:sub>\n approach at baseline and throughout LBPP and LBNP. Impedance cardiography\u2010derived thoracic fluid content (TFC) was used as a proxy of CBV. LBPP induced a progressive increase in TFC (\n P\u00a0<\/jats:italic>\n <\u00a00.001); however DL\n CO<\/jats:sub>\n did not change (\n P\u00a0=\u00a0<\/jats:italic>\n 0.589) due to a reciprocal increase in\n V<\/jats:italic>\n c<\/jats:sub>\n (\n P\u00a0=\u00a0<\/jats:italic>\n 0.009) and a decrease in\n D<\/jats:italic>\n m,CO<\/jats:sub>\n (\n P\u00a0<\/jats:italic>\n <\u00a00.001). In contrast LBNP elicited graded reductions in TFC (\n P\u00a0<\/jats:italic>\n <\u00a00.001), DL\n CO<\/jats:sub>\n (\n P\u00a0<\/jats:italic>\n <\u00a00.001) and\n V<\/jats:italic>\n c<\/jats:sub>\n (\n P\u00a0<\/jats:italic>\n <\u00a00.001), with no change in\n D<\/jats:italic>\n m,CO<\/jats:sub>\n (\n P\u00a0=\u00a0<\/jats:italic>\n 0.610). Across LBPP and LBNP changes in TFC were associated with the corresponding changes in DL\n CO<\/jats:sub>\n (\n P\u00a0<\/jats:italic>\n <\u00a00.001) and\n V<\/jats:italic>\n c<\/jats:sub>\n (\n P\u00a0<\/jats:italic>\n <\u00a00.001), and\n D<\/jats:italic>\n m,CO<\/jats:sub>\n (\n P\u00a0<\/jats:italic>\n <\u00a00.044). Collectively these findings demonstrate that, in the supine position, pulmonary gas transfer is dynamically influenced by relatively small perturbations in CBV, primarily via alterations in\n V<\/jats:italic>\n c<\/jats:sub>\n .\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Central blood volume (CBV) and pulmonary artery pressure are key determinants of pulmonary diffusing capacity for carbon monoxide (DL\n CO<\/jats:sub>\n ) and its components, capillary blood volume (\n V<\/jats:italic>\n c<\/jats:sub>\n ) and membrane diffusing capacity (\n D<\/jats:italic>\n m,CO<\/jats:sub>\n ); however the role of CBV in DL\n CO<\/jats:sub>\n and its components has not yet been elucidated.\n <\/jats:p>\n <\/jats:list-item>\n \n \n During lower body positive pressure (increased CBV), DL\n CO<\/jats:sub>\n did not change due to reciprocal increases in\n V<\/jats:italic>\n c<\/jats:sub>\n and decreases in\n D<\/jats:italic>\n m,CO<\/jats:sub>\n .\n <\/jats:p>\n <\/jats:list-item>\n \n \n During lower body negative pressure (central hypovolaemia), DL\n CO<\/jats:sub>\n significantly declined, secondary to a decrease in\n V<\/jats:italic>\n c<\/jats:sub>\n .\n <\/jats:p>\n <\/jats:list-item>\n \n \n DL\n CO<\/jats:sub>\n and\n V<\/jats:italic>\n c<\/jats:sub>\n exhibited non\u2010linear relationships with thoracic fluid content (TFC, an index of CBV), whereas\n D<\/jats:italic>\n m,CO<\/jats:sub>\n demonstrated a negative linear relationship with TFC.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Our findings demonstrate that TFC\u2010mediated\n V<\/jats:italic>\n c<\/jats:sub>\n expansion alone is insufficient to augment DL\n CO<\/jats:sub>\n , whereas central hypovolaemia reduces DL\n CO<\/jats:sub>\n primarily via reduced capillary distention\/recruitment.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp291422","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:32:38Z","timestamp":1787113958000},"page":"7957-7970","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential effects of central blood volume loading and unloading on pulmonary diffusing capacity in humans"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-0446","authenticated-orcid":false,"given":"Andrew W.","family":"D'Souza","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-5013","authenticated-orcid":false,"given":"Andrew R.","family":"Brotto","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport, and Recreation University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Williams","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport, and Recreation University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3106-6245","authenticated-orcid":false,"given":"Chuanyi","family":"Foo","sequence":"additional","affiliation":[{"name":"Faculty of Kinesiology, Sport, and Recreation University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Bok","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desi 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