Cerebral blood flow and metabolism under conditions of simulated avalanche burial in humans: The triple H syndrome
Abstract Avalanche burial exposes individuals to a combination of hypothermia, hypercapnia and hypoxia. We investigated the impact of mild hypothermia on cerebrovascular function during room‐air 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‐L) and glial fibrillary acidic protein (GFAP), whereas duplex ultrasound was used to quantify global cerebral blood flow (CBF), cerebral oxygen delivery (CDO 2 ), oxygen extraction fraction (OEF) and metabolic rate of oxygen (CMRO 2 ) before and during mild hypothermia (−1.8 ± 0.6°C; oesophageal thermistor) via ∼7°C water immersion. Progressive hypercapnic hypoxia was imposed in 2 min stages (−5 mmHg ; +2 mmHg ) to a maximal stimulus of 40 mmHg and +20 mmHg . Hypothermia increased arterial O 2 content and blood pressure and reduced . Progressive hypercapnic hypoxia elevated CDO 2 but reduced CMRO 2 (all P < 0.05). Mild hypothermia reduced CBF ( P < 0.05) and CMRO 2 in 11 out of the 13 volunteers ( P = 0.16). When comparing normothermia and hypothermia during progressive hypercapnic hypoxia or with matched and , both OEF and CMRO 2 were reduced ( P < 0.05), whereas the hypothermia‐induced 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 2 is mediated by temperature. Tau, Nf‐L and GFAP were reduced following hypothermia during room‐air breathing and during hypercapnic hypoxia; hypothermia also led to reduced cerebral release of pro‐inflammatory cytokines (i.e. interleukin 1β; P = 0.02). 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. image Key points 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. Core body cooling (∼1.8°C) lowers the brain's metabolic rate of oxygen, suggesting reduced energy demand in the brain. Hypothermia decreases cerebral blood flow, but this effect is mainly due to reduced carbon dioxide levels (hypocapnia) – not temperature or metabolism alone. When carbon dioxide is matched to normal body temperature levels, the drop in blood flow disappears. Markers of brain injury (tau, neurofilament light (Nf‐L) and glial fibrillary acidic protein (GFAP)) and inflammation (e.g. interleukin 1β (IL‐1β)) decrease during hypothermia, suggesting a potential neuroprotective effect.
Authors
- Connor A. Howe (ORCID: https://orcid.org/0000-0002-1133-2444)
- Gustavo Vizcardo‐Galindo (ORCID: https://orcid.org/0000-0002-8131-8808)
- Jay M. J. R. Carr (ORCID: https://orcid.org/0000-0001-7236-1348)
- Mike Tymko (ORCID: https://orcid.org/0009-0003-8454-1751)
- Valerie C. Cates (ORCID: https://orcid.org/0000-0002-1384-1410)
- Philip N. Ainslie (ORCID: https://orcid.org/0000-0001-6560-222X)
- Anthony L. Marullo (ORCID: https://orcid.org/0000-0002-1460-7167)
- Mypinder S. Sekhon (ORCID: https://orcid.org/0000-0002-4487-301X)
- Trevor A. Day (ORCID: https://orcid.org/0000-0001-7102-4235)
- Travis D. Gibbons (ORCID: https://orcid.org/0000-0003-3893-9948)
- Andrew R. Steele
- Ryan L. Hoiland
Institutions
- Eurac Research (IT)
- University of British Columbia (CA)
- University College Cork (IE)
- Vancouver General Hospital (CA)
- Institute of Mountain Emergency Medicine (IT)
- Department of Physiological Sciences (RU)
- University of Guelph (CA)
- Okanagan University College (CA)
- Mount Royal University (CA)
Publication Details
- Journal
- The Journal of Physiology
- Published
- 2026-09-16
- DOI
- https://doi.org/10.1113/jp291528
- Primary Topic
- Thermal Regulation in Medicine
- Type
- article
- Field-Weighted Citation Impact
- 0.00