Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: implications for cerebral bioenergetic function

Damian Bailey*, Anthony R. Bain, Ryan L. Hoiland, Otto F. Barak, Ivan Drvis, Benjamin Stacey, Angelo Iannetelli, Gareth W. Davison, Rasmus H. Dahl, Ronan M. G. Berg, David B. MacLeod, Zeljko Dujic, Philip Ainslie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We examined to what extent apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox-regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (6 men, 4 women) performed two maximal dry apnoeas preceded by, [1] normoxic normoventilation resulting in severe end-apnoea hypoxaemic hypercapnia and [2] hyperoxic hyperventilation designed to ablate hypoxaemia resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (A·-, electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (NO, tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P = <0.001). Apnoea generally increased gCBF (all P = <0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015 to 0.044). This was associated with a general net cerebral output (v>a) of A·- that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite (〖"NO" 〗_"2" ^"-" ) uptake (a>v) and gCBF (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of NO consistent with elevated cerebral oxidative-nitrosative stress (OXNOS). In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P = >0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral OXNOS.
Original languageEnglish
Article numberJP285555
Number of pages26
JournalJournal of Physiology
Volume00
Issue number00
Early online date13 Feb 2024
DOIs
Publication statusE-pub ahead of print - 13 Feb 2024

Keywords

  • oxygen
  • carbon dioxide
  • free radicals
  • nitric oxidie
  • cerebral blood flow

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