Cerebral metabolism, oxidation and inflammation in severe passive hyperthermia with and without respiratory alkalosis

Abstract

Key points It was unknown whether respiratory alkalosis impacts the global cerebral metabolic response as well as the cerebral pro‐oxidation and inflammatory response in passive hyperthermia. This study demonstrated that the cerebral metabolic rate was increased by ∼20% with passive hyperthermia of up to +2°C oesophageal temperature, and this response was unaffected by respiratory alkalosis. Additionally, the increase in cerebral metabolism did not significantly impact the net cerebral release of oxidative and inflammatory markers. These data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, but it does markedly increase the cerebral metabolic rate, independently of PnormalaCO2. Abstract There is limited information concerning the impact of arterial PnormalCO2/pH on heat‐induced alteration in cerebral metabolism, as well as on the cerebral oxidative/inflammatory burden of hyperthermia. Accordingly, we sought to address two hypotheses: (1) passive hyperthermia will increase the cerebral metabolic rate of oxygen (CMRO2) consistent with a combined influence of Q10 and respiratory alkalosis; and (2) the net cerebral release of pro‐oxidative and pro‐inflammatory markers will be elevated in hyperthermia, particularly in poikilocapnic hyperthermia. Healthy young men (n = 6) underwent passive heating until an oesophageal temperature of 2°C above resting was reached. At 0.5°C increments in core temperature, CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery–jugular venous oxygen content difference (cannulation). Net cerebral glucose/lactate exchange, and biomarkers of oxidative and inflammatory stress were also measured. At +2.0°C oesophageal temperature, arterial PnormalCO2 was restored to normothermic values using end‐tidal forcing. The primary findings were: (1) while CMRO2 was increased (P < 0.05) by ∼20% with hyperthermia of +1.5–2.0°C, this was not influenced by respiratory alkalosis, and (2) although biomarkers of pro‐oxidation and pro‐inflammation were systemically elevated in hyperthermia (P < 0.05), there were no differences in the trans‐cerebral exchange kinetics. These novel data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, despite it markedly increasing CMRO2, irrespective of arterial pH.

Influence of the mode of heating on cerebral blood flow, non‐invasive intracranial pressure and thermal tolerance in humans

“…2009; Bain et al . 2013, 2020). As such, the appropriate control of cerebral blood flow (CBF) in the heat is essential, especially because the brain's capacity to extract oxygen is limited (Bain & Ainslie, 2014).…”

“…2008; Bain et al . 2020). The dose of heating required to elicit hyperventilation also appears to be dependent on whether heating is active or passive (Tsuji et al .…”

“…2002 a ; Bain et al . 2020), it seems plausible that CBF responses to heating might partly influence volitional thermal tolerance during both exercise and passive heat exposure. Elucidating the mechanisms of CBF control leading up to thermal intolerance provides a novel approach to explore whether brain temperature per s e is the criterion homeostatically regulated variable under different forms of heat stress, and whether CBF regulation plays an integral role.…”

Does sauna bathing protect against dementia?

“…The elderly and other groups with compromised thermoregulatory control are especially vulnerable during severe passive heat stress ( Bain et al, 2015 ). Among young people the effects of moderate and high thermal stress on the brain may be counterbalanced by cardiovascular, cerebral and metabolic alterations ( Bain et al, 2020 , Gibbons et al, 2020 ).…”

Hyperthermia: The hotter the body, the hungrier the brain?

“…Firstly, they test whether the increase in CMRO 2 is affected by the increase in body temperature and thus what the temperature sensitivity of the metabolic processes in the brain is and secondly, they investigate whether there is an elevated release of pro‐oxidative and pro‐inflammatory markers during passive hyperthermia, with or without hypocapnia (Bain et al . 2020).…”