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Abstract: Progressive neurological depression leading to coma was produced in unanesthetized rats at a constant level of hypoglycemia induced by insulin. High‐energy phosphate concentrations in brain remained normal during hypoglycemic lethargy, but ATP declined by 6% during stupor and by 40% during coma that was characterized by an isoelectric EEG. Cerebral blood flow (CBF) remained normal during hypoglycemia whereas the cerebral metabolic rates for oxygen (CMRo 2 ) and glucose (CMR glucose ) decreased by 45 and 73%, respectively, indicating oxidation of nonglucose fuels. A plot of CMRo 2 and CMR glucose versus plasma glucose indicated increasing oxidation of alternate substrates (elevated CMRo 2 /CMR glucose ) at plasma glucose concentrations below 2.5 m m . The cerebral uptake of β‐hydroxybutyrate increased during hypoglycemic stupor and its complete oxidation could account for the CMRo 2 in excess of glucose utilization. Brain ammonia, a byproduct of amino acid metabolism, reached a level during hypoglycemic coma sufficient to produce coma in normoglycemic animals. The rate and degree of recovery after glucose administration depended on the duration of hypoglycemia and the pretreatment neurological state of the animal. Following 10 min of glucose infusion, ATP levels that were modestly depressed in stuporous rats recovered fully, paralleling the animals' apparently full neurological recovery. Rats that had been in hypoglycemic coma for 1 min or less fully recovered high‐energy phosphate concentrations in brain. However, when normalization of plasma glucose was delayed for more than 1 min of coma, the CMRo 2 remained depressed, CBF decreased to 40% of control, and high‐energy substrates failed to normalize. In keeping with the depression of oxidative metabolism and blood flow, neurological function and the EEG remained abnormal even after 1 h of glucose infusion. The findings suggest that irreversible brain injury may develop within the first minutes of hypoglycemic coma.
Ghajar et al. (Mon,) studied this question.