INTERPLAY BETWEEN BRAIN OXYGENATION AND THE DEVELOPMENT OF HYPOTHERMIA IN ENDOTOXIC SHOCK

• Published in: Shock (Augusta, Ga.) Vol. 61; no. 6; p. 861
• Main Authors: Moretti, Eduardo H, Lino, Caroline A, Steiner, Alexandre A
• Format: Journal Article
• Language: English
• Published: United States 01.06.2024
• Subjects: Animals; Brain - metabolism; Hypothermia - metabolism; Hypothermia - physiopathology; Lipopolysaccharides; Male; Oxygen - metabolism; Oxygen Consumption - physiology; Rats; Rats, Wistar; Shock, Septic - metabolism; Shock, Septic - physiopathology
• ISSN: 1540-0514
• DOI: 10.1097/SHK.0000000000002350

There is evidence to suggest that the hypothermia observed in the most severe cases of systemic inflammation or sepsis is a regulated response with potential adaptive value, but the mechanisms involved are poorly understood. Here, we investigated the interplay between brain oxygenation (assessed by tissue P o2 ) and the development of hypothermia in unanesthetized rats challenged with a hypotension-inducing dose of bacterial LPS (1 mg/kg i.v.). At an ambient temperature of 22°C, oxygen consumption (V̇O 2 ) began to fall only a few minutes after the LPS injection, and this suppression in metabolic rate preceded the decrease in core temperature. No reduction in brain P o2 was observed prior to the development of the hypometabolic, hypothermic response, ruling out the possibility that brain hypoxia served as a trigger for hypothermia in this model. Brain P o2 was even increased. Such an improvement in brain oxygenation could reflect either an increased O 2 delivery or a decreased O 2 consumption. The former explanation seems unlikely because blood flow (cardiac output) was being progressively decreased during the recording period. On the other hand, the decrease in V̇O 2 usually preceded the rise in P o2 , and an inverse correlation between V̇O 2 and brain P o2 was consistently observed. These findings do not support the existence of a closed-loop feedback relationship between brain oxygenation and hypothermia in systemic inflammation. The data are consistent with a feedforward mechanism in which hypothermia is triggered (possibly by cryogenic inflammatory mediators) in anticipation of changes in brain oxygenation to prevent the development of tissue hypoxia.