Hypoxia and beta-hydroxybutyrate acutely reduce glucose extraction by the brain in anesthetized dogs.
Induced ketosis may acutely prolong hypoxic tolerance by altering glucose and (or) beta-hydroxybutyrate extraction by the brain. Anesthetized dogs were ventilated and instrumental for arterial and cerebral venous blood sampling, taken during baseline, infusion, test, and recovery periods. Each dog received one of four different beta-hydroxybutyrate doses and 25 min of either a normoxic or hypoxic (8% oxygen) test period. Arterial glucose and beta-hydroxybutyrate were stable in the saline and 3 mg.kg-1 x min-1 beta-hydroxybutyrate infusion groups, but glucose declined and beta-hydroxybutyrate increased in the 10 and 20 mg.kg-1 x min-1 beta-hydroxybutyrate infusion groups. During normoxia glucose arteriovenous differences across the brain decreased significantly only in the 20 mg.kg-1 x min-1 beta-hydroxybutyrate infusion groups, and during hypoxia the differences decreased for all groups. beta-Hydroxybutyrate arteriovenous differences tended to increase with a 100-fold increase in beta-hydroxybutyrate concentrations, but the trend was not statistically significant. Hypoxia further decreased glucose extraction, but did not change beta-hydroxybutyrate extraction. We conclude that beta-hydroxybutyrate may protect during hypoxia by depressing glucose uptake and consumption rather than by acting as an alternative cerebral energy substrate.
Chang
A S
AS
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
D'Alecy
L G
LG
D020155:3-Hydroxybutyric Acid; D000758:Anesthesia; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics; D006885:Hydroxybutyrates / Q000097:blood / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male
D001786:Blood Glucose; D006885:Hydroxybutyrates; D005947:Glucose; D020155:3-Hydroxybutyric Acid