{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:04:20Z","timestamp":1792029860952,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2020\u201005760"],"award-info":[{"award-number":["2020\u201005760"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["HL077450"],"award-info":[{"award-number":["HL077450"]}],"id":[{"id":"10.13039\/100000009","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":[[2023,12]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Passive hyperthermia causes cerebral hypoperfusion primarily from heat\u2010induced respiratory alkalosis. However, despite the cerebral hypoperfusion, it is possible that the mild alkalosis might help to attenuate cerebral inflammation. In this study, the cerebral exchange of extracellular vesicles (microvesicles), which are known to elicit pro\u2010inflammatory responses when released in conditions of stress, were examined in hyperthermia with and without respiratory alkalosis. Ten healthy male adults were heated passively, using a warm water\u2010perfused suit, up to core temperature\u00a0+\u00a02\u00b0C. Blood samples were taken from the radial artery and internal jugular bulb. Microvesicle concentrations were determined in platelet\u2010poor plasma via cells expressing CD62E (activated endothelial cells), CD31<jats:sup>+<\/jats:sup>\/CD42b<jats:sup>\u2212<\/jats:sup> (apoptotic endothelial cells), CD14 (monocytes) and CD45 (pan\u2010leucocytes). Cerebral blood flow was measured via duplex ultrasound of the internal carotid and vertebral arteries to determine cerebral exchange kinetics. From baseline to poikilocapnic (alkalotic) hyperthermia, there was no change in microvesicle concentration from any cell origin measured (<jats:italic>P<\/jats:italic>\u2010values all &gt;0.05). However, when blood CO<jats:sub>2<\/jats:sub> tension was normalized to baseline levels in hyperthermia, there was a marked increase in cerebral uptake of microvesicles expressing CD62E (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.028), CD31<jats:sup>+<\/jats:sup>\/CD42b<jats:sup>\u2212<\/jats:sup> (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) and CD14 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.031) compared with baseline, corresponding to large increases in arterial but not jugular venous concentrations. In a subset of seven participants who underwent hypercapnia and hypocapnia in the absence of heating, there was no change in microvesicle concentrations or cerebral exchange, suggesting that hyperthermia potentiated the CO<jats:sub>2<\/jats:sub>\/pH\u2010mediated cerebral uptake of microvesicles. These data provide insight into a potential beneficial role of respiratory alkalosis in heat stress.\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\/tjp15827-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 hyperthermia\u2010induced hyperventilatory response is observed in most humans, despite causing potentially harmful reductions in cerebral blood flow.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We tested the hypothesis that the respiratory\u2010induced alkalosis is associated with lower circulating microvesicle concentrations, specifically in the brain, despite the reductions in blood flow.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At core temperature\u00a0+\u00a02\u00b0C with respiratory alkalosis, microvesicles derived from endothelial cells, monocytes and leucocytes were at concentrations similar to baseline in the arterial and cerebral venous circulation, with no changes in cross\u2010brain microvesicle kinetics.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>However, when core temperature was increased by 2\u00b0C with CO<jats:sub>2<\/jats:sub>\/pH normalized to resting levels, there was a marked cerebral uptake of microvesicles derived from endothelial cells and monocytes. The CO<jats:sub>2<\/jats:sub>\/pH\u2010mediated alteration in cerebral microvesicle uptake occurred only in hyperthermia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These new findings suggest that the heat\u2010induced hyperventilatory response might serve a beneficial role by preventing potentially inflammatory microvesicle uptake in the brain.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285265","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T09:33:09Z","timestamp":1700213589000},"page":"5601-5616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cerebral uptake of microvesicles occurs in normocapnic but not hypocapnic passive hyperthermia in young healthy male adults"],"prefix":"10.1113","volume":"601","author":[{"given":"Khushali","family":"Parikh","sequence":"first","affiliation":[{"name":"Faculty of Human Kinetics Department of Kinesiology University of Windsor  Windsor ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5111-3286","authenticated-orcid":false,"given":"Brooke R.","family":"Shepley","sequence":"additional","affiliation":[{"name":"Faculty of Human Kinetics Department of Kinesiology University of Windsor  Windsor ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Tymko","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia  Kelowna BC Canada"},{"name":"Department of Human Health and Nutritional Sciences College of Biological Science University of Guelph  Guelph ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie G.","family":"Hijmans","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology University of Colorado Boulder  Boulder CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan L.","family":"Hoiland","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia  Kelowna BC Canada"},{"name":"Division of Critical Care Medicine Department of Medicine Faculty of Medicine University of British Columbia  Vancouver BC Canada"},{"name":"Division of Neurosurgery Department of Surgery Faculty of Medicine University of British Columbia  Vancouver BC Canada"},{"name":"International Collaboration on Repair Discoveries University of British Columbia  Vancouver BC Canada"},{"name":"Collaborative Entity for Researching Brain Ischemia University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9372-5083","authenticated-orcid":false,"given":"Christopher A.","family":"Desouza","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology 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