Cerebral oxidative metabolism during hypothermia and circulatory arrest in newborn dogs.
To ascertain the alterations in cerebral oxidative and energy metabolism that occur during hypothermic circulatory arrest, nitrous oxide-anesthetized, paralyzed, and artificially ventilated newborn dogs were surface cooled to 18-20 degrees C, after which their hearts were arrested with KCl. At 10, 30, 60, and 105 min of circulatory arrest, their brains were prepared by in situ freezing for the regional analysis of glycolytic intermediates and high-energy phosphate reserves. Hypothermia alone was associated with optimal preservation of labile metabolites in brain, even in caudal brainstem and cerebellum, compared with barbiturate-anesthetized littermates. After onset of hypothermic circulatory arrest, glucose decreased progressively in cerebral cortex, caudate nucleus, hippocampus, and subcortical white matter to negligible levels by 30 min. Pyruvate increased transiently (+50%) at 10 min, whereas lactate increased and plateaued (10-11 mmol/kg) at 30 min. The disproportionate increases in pyruvate and lactate resulted in a progressive rise in the lactate/pyruvate ratio. Phosphocreatine fell precipitously to < 0.5 mmol/kg in all structures, with a preservation of ATP for the first 10 min of cerebral ischemia. Thereafter, ATP decreased to < 0.1 mmol/kg in cerebral cortex and between 0.1 and 0.2 mmol/kg in caudate nucleus, hippocampus, and white matter. Total adenine nucleotides (ATP+ADP+AMP) were partially depleted by 30 min in the gray matter structures but were unchanged from control for 60 min in white matter. The findings showed a direct correlation between preservation of cerebral energy stores during hypothermic circulatory arrest and the selective resistance of subcortical white matter to ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Yager
J Y
JY
Department of Pediatrics (Neurology and Neonatology), Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033.
Brucklacher
R M
RM
Mujsce
D J
DJ
Vannucci
R C
RC
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism; D006019:Glycolysis; D006323:Heart Arrest / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007035:Hypothermia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D010101:Oxygen Consumption