Metabolism of glucose, glycogen, and high-energy phosphates during complete cerebral ischemia. A comparison of normoglycemic, chronically hyperglycemic diabetic, and acutely hyperglycemic nondiabetic rats.
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BACKGROUND
Increases in brain glucose will worsen outcome after global cerebral ischemia, and some experimental evidence suggests that the duration of hyperglycemia also may influence outcome. Different types of hyperglycemia were studied to identify metabolic differences that might account for alterations in postischemic outcome.
METHODS
Ninety pentobarbital-anesthetized Sprague-Dawley rats were divided into three groups: normoglycemic nondiabetic rats (N) (n = 30), chronically hyperglycemic diabetic rats (HD) (n = 30), and acutely hyperglycemic, glucose-infused nondiabetic rats (HN) (n = 30). These groups were further subdivided into groups of six rats each that received 0, 2.5, 5, 10, or 15 min of complete cerebral ischemia (potassium chloride--induced cardiac arrest). Brains were excised after 10-kW focused microwave radiation and metabolites were measured using enzymatic fluorometric techniques.
RESULTS
At all study intervals, plasma glucose concentrations in HD and HN were fourfold greater than in N. Before ischemia, brain glucose concentrations in all groups were proportional to plasma glucose concentrations; however, brain glycogen concentrations did not differ among groups. After the onset of ischemia, there was an immediate diminution of brain glucose, glycogen, adenosine triphosphate (ATP), and phosphocreatine that in all cases was most pronounced during the initial 2.5 min of ischemia. Consumption of carbohydrate stores and lactate production were greater in HD and HN than in N. HD had lesser preischemic ATP concentrations and energy charges relative to N and HN (P < 0.05), perhaps reflecting their disease state; however, at 2.5 min of ischemia, the relationship of ATP concentrations and energy charges was HN > HD > N (P < 0.05 among all). In all groups, ATP and phosphocreatine were more than 96% depleted by 10 min of ischemia. With few exceptions (ATP concentrations and energy charges before ischemia and at 2.5 min, and lactate concentration in HD < HN at 15 min), there were no measured metabolic differences between HD and HN.
CONCLUSIONS
In these studies, the duration of hyperglycemia did not affect intraischemic carbohydrate consumption. At short durations of ischemia (2.5 min), both HD and HN groups had greater intraischemic ATP concentrations and energy charges than N; however, at longer durations of ischemia (> 5.0 min), high-energy phosphate depletion was similarly severe in all groups. These studies suggest that energy failure is not the origin of worse postischemic neurologic injury in hyperglycemic subjects, nor does energy failure readily explain reported differences between acutely and chronically hyperglycemic subjects exposed to global cerebral ischemia.
