Effect of altered availability of energy-yielding substrates upon survival from hypoxia in mice.

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Abstract
The duration of survival during a hypoxic or ischemic incident can be altered by barbiturate anesthesia. If the effect on the brain is due to a reduction in lactic acid production by hypoxia, a similar protective effect may be produced by altering substrate availability. Groups of mice (6) were subjected to hypoxia (4-5% O2, balance N2) at 30 to 35.degree. C: hypoglycemia was induced by 2 U [units] insulin injected in 30 min prior to hypoxia; ketotic hypoglycemia was induced by fasting 85-90 h prior to hypoxia; hyperglycemia was induced by i.v. dextrose; diabetic-ketotic-hyperglycemia was induced by i.v. alloxan 5 days prior to hypoxia; 1 group was given both the insulin and dextrose in the above sequence. In controls, saline was given i.v. or i.p. when appropriate. The mean survival time for ketotic-hypoglycemic and diabetic-ketotic-hyperglycemic mice was significantly higher than control. The mean survival time for the insulin-hypoglycemic mice was significantly lower than control. The remaining groups showed no difference from control. The observed improvement in survival time from hypoxia seen in the ketotic animals suggests that during hypoxia, the brain metabolizes ketones selectively and minimizes the production of lactic acid to maintain neuronal viability.