{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:02:04Z","timestamp":1789581724493,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Avalanche burial exposes individuals to a combination of hypothermia, hypercapnia and hypoxia. We investigated the impact of mild hypothermia on cerebrovascular function during room\u2010air breathing and progressive hypercapnic hypoxia. In 14 participants (6 females) the radial artery and internal jugular vein were catheterized to measure blood gases, intravascular pressure, biomarkers of neurovascular damage (tau, neurofilament light (Nf\u2010L) and glial fibrillary acidic protein (GFAP), whereas duplex ultrasound was used to quantify global cerebral blood flow (CBF), cerebral oxygen delivery (CDO\n 2<\/jats:sub>\n ), oxygen extraction fraction (OEF) and metabolic rate of oxygen (CMRO\n 2<\/jats:sub>\n ) before and during mild hypothermia (\u22121.8 \u00b1 0.6\u00b0C; oesophageal thermistor) via \u223c7\u00b0C water immersion. Progressive hypercapnic hypoxia was imposed in 2 min stages (\u22125 mmHg ; +2 mmHg ) to a maximal stimulus of 40 mmHg and +20 mmHg . Hypothermia increased arterial O\n 2<\/jats:sub>\n content and blood pressure and reduced . Progressive hypercapnic hypoxia elevated CDO\n 2<\/jats:sub>\n but reduced CMRO\n 2<\/jats:sub>\n (all\n P<\/jats:italic>\n < 0.05). Mild hypothermia reduced CBF (\n P<\/jats:italic>\n < 0.05) and CMRO\n 2<\/jats:sub>\n in 11 out of the 13 volunteers (\n P<\/jats:italic>\n \u00a0=\u00a00.16). When comparing normothermia and hypothermia during progressive hypercapnic hypoxia or with matched and , both OEF and CMRO\n 2<\/jats:sub>\n were reduced (\n P<\/jats:italic>\n < 0.05), whereas the hypothermia\u2010induced reduction in CBF was abolished. At least in the temporal domains of the current study during mild hypothermia it seems that hypocapnia is the primary mechanism behind the reduction in CBF, whereas the suppression of CMRO\n 2<\/jats:sub>\n is mediated by temperature. Tau, Nf\u2010L and GFAP were reduced following hypothermia during room\u2010air breathing and during hypercapnic hypoxia; hypothermia also led to reduced cerebral release of pro\u2010inflammatory cytokines (i.e. interleukin 1\u03b2;\n P<\/jats:italic>\n \u00a0=\u00a00.02). These findings suggest that reductions in core temperature and alterations in blood gases that may occur during avalanche burial distinctly impact cerebral perfusion, metabolism and selected biomarkers of neurovascular damage and inflammation.\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 The study simulates avalanche burial (hypothermia + low oxygen + high carbon dioxide) in healthy humans and shows that these conditions significantly alter cerebral blood flow, oxygen delivery and brain metabolism.<\/jats:p>\n <\/jats:list-item>\n \n Core body cooling (\u223c1.8\u00b0C) lowers the brain's metabolic rate of oxygen, suggesting reduced energy demand in the brain.<\/jats:p>\n <\/jats:list-item>\n \n Hypothermia decreases cerebral blood flow, but this effect is mainly due to reduced carbon dioxide levels (hypocapnia) \u2013 not temperature or metabolism alone. When carbon dioxide is matched to normal body temperature levels, the drop in blood flow disappears.<\/jats:p>\n <\/jats:list-item>\n \n Markers of brain injury (tau, neurofilament light (Nf\u2010L) and glial fibrillary acidic protein (GFAP)) and inflammation (e.g. interleukin 1\u03b2 (IL\u20101\u03b2)) decrease during hypothermia, suggesting a potential neuroprotective effect.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp291528","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:06:37Z","timestamp":1789578397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebral blood flow and metabolism under conditions of simulated avalanche burial in humans: The triple H syndrome"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-2444","authenticated-orcid":false,"given":"Connor A.","family":"Howe","sequence":"first","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia \u2013 Okanagan Campus, School of Health and Exercise Science Kelowna Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7236-1348","authenticated-orcid":false,"given":"Jay M. 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R.","family":"Carr","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia \u2013 Okanagan Campus, School of Health and Exercise Science Kelowna Canada"},{"name":"Institute of Mountain Emergency Medicine Eurac Research Bolzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan L.","family":"Hoiland","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis D.","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia \u2013 Okanagan Campus, School of Health and Exercise Science Kelowna Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Steele","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia \u2013 Okanagan Campus, School of Health and Exercise Science Kelowna Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8131-8808","authenticated-orcid":false,"given":"Gustavo A.","family":"Vizcardo\u2010Galindo","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia \u2013 Okanagan Campus, School of Health and Exercise Science Kelowna Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Tymko","sequence":"additional","affiliation":[{"name":"Integrative Cerebrovascular and Environmental Physiology SB Laboratory, Department of Human Health and Nutritional Sciences, College of Biological Science University of Guelph Guelph Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8454-1751","authenticated-orcid":false,"given":"Tison","family":"Schoenthal","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics Vancouver General Hospital, University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie C.","family":"Cates","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology Mount Royal University Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"Marullo","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology Mount Royal University Calgary Canada"},{"name":"Department of Physiology University College Cork Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-4235","authenticated-orcid":false,"given":"Trevor A.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology Mount Royal University Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mypinder S.","family":"Sekhon","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology and Therapeutics Vancouver General Hospital, University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6560-222X","authenticated-orcid":false,"given":"Philip N.","family":"Ainslie","sequence":"additional","affiliation":[{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia \u2013 Okanagan Campus, School of Health and Exercise Science Kelowna Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"9","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1042\/CS20130343","article-title":"Stability of cerebral metabolism and substrate availability in humans during hypoxia and hyperoxia","volume":"126","author":"Ainslie P. 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