GLOBAL CEREBRAL-ISCHEMIA IN PIGLETS UNDER CONDITIONS OF MILD AND DEEP HYPOTHERMIA

Background and Purpose: To investigate the effects of hypothermia on the rate of change and degree of recovery of brain adenosine triphosphate and phosphocreatine concentrations and intracellular pH, we have developed a model that allows phosphorus nuclear magnetic resonance spectroscopy of the intact piglet brain during circulatory arrest. Methods: Three groups of piglets were studied. Three control animals underwent cardiopulmonary bypass at normothermia for 1 hour; five group 1 animals underwent bypass at a brain temperature of 15-degrees-C, followed by a period of circulatory arrest such that adenosine triphosphate was absent for 21 minutes, followed by 1 hour of reperfusion; and five group 2 animals underwent bypass at a brain temperature of 37-degrees-C, followed by a period of circulatory arrest such that adenosine triphosphate was absent for 21 minutes, followed by reperfusion for 1 hour. Results: Control animals showed no significant metabolic effects of bypass. Group 1 animals showed a slower decay of the adenosine triphosphate and phosphocreatine concentrations than group 2 animals, consistent with a lower metabolic rate, and had a higher pH at the onset of ischemia. Recovery of the adenosine triphosphate concentration was significantly better in group 1 animals (95%) than in group 2 animals (30%) (p < 0.02), and recovery of the phosphocreatine concentration was also better in group 1 animals (93%) than in group 2 animals (32%) (p < 0.02). Intracellular pH recovered in group 1 animals, but not in group 2 animals. Regional biochemical assays of metabolites performed in the group 2 piglets and in five pilot piglets exposed to deep hypothermia generally confirmed the spectroscopic findings but demonstrated considerable regional variation, especially in the group 2 piglets' brains. Conclusions: We conclude that hypothermia exerts a protective effect on the piglet brain during global ischemia even after the adenosine triphosphate pool has been completely depleted.