Integrated respiratory chemoreflex‐mediated regulation of cerebral blood flow in hypoxia: Implications for oxygen delivery and acute mountain sickness

Shigehiko Ogoh, Takuro Washio, Benjamin S. Stacey, Hayato Tsukamoto, Angelo Iannetelli, Thomas S. Owens, Thomas A. Calverley, Lewis Fall, Christopher J Marley, Shotaro Saito, Hironori Watanabe, Takeshi Hashimoto, Soichi Ando, Tadayoshi Miyamoto, Damian M. Bailey

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of the present study was to determine to what extent hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF), oxygen delivery (CDO2) and corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy males were randomly assigned single-blind to 7 h passive exposure to both normoxia (21% O2) and hypoxia (12% O2). The peripheral and central respiratory chemoreflex, internal carotid (ICA), external carotid (ECA), and vertebral (VA) artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in ICA CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, VA and ECA CDO2 were preserved that in the former was due to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P <0.001) whereas the central respiratory chemoreflex remained unchanged (P >0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (LLS, r = 0.546∼0.709, P = 0.004∼0.043; ESQ-C, r = 0.587∼0.771, P = 0.001∼0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that selectively maintains CDO2 in the posterior but not anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilation may represent a hitherto unexplored hemodynamic risk factor implicated in the pathophysiology of AMS.
Original languageEnglish
Article numberEP089660
Pages (from-to)1922-1938
Number of pages17
JournalExperimental Physiology
Volume106
Issue number9
Early online date27 Jul 2021
DOIs
Publication statusE-pub ahead of print - 27 Jul 2021

Keywords

  • hypoxia
  • cerebral blood flow
  • oxygen delivery
  • respiratory chemoreflex
  • acute mountain sickness

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