Effects of hypoglycemia on the cerebral circulation in awake goats.

We electromagnetically measured blood flow to one cerebral hemisphere and determined cerebrovascular reactivity to vasoconstrictor and vasodilator stimuli during normoglycemia and insulin-induced hypoglycemia in unanesthetized goats. Control blood glucose concentration was 84 +/- 4 mg, and insulin, injected intravenously, decreased glycemia with a concomitant increment in cerebral blood flow and reduction in cerebrovascular resistance in all the animals. When glycemia decreased to 60 to 65 mg/dl, the animals began to show signs of increased adrenergic activity, and when it decreased to less than 30 mg/dl, they showed signs of CNS depression. Cerebral blood flow began to rise significantly at a glycemia of 50 to 55 mg/dl, and progressively increased to reach an increment of 36% +/- 4% when glycemia was less than 30 mg/dl. Norepinephrine (0.3 to 9 micrograms), tyramine (50 to 500 micrograms), and 5-hydroxytryptamine (0.1 to 9 micrograms) reduced cerebral blood flow, and this effect was lower during severe hypoglycemia. Acetylcholine (0.01 to 1 microgram), isoproterenol (0.03 to 3 micrograms), diazoxide (0.3 to 9 mg), and inhalation of 10% CO2 in air increased cerebral blood flow, and this effect was also lower during severe hypoglycemia. The results show that insulin-induced hypoglycemia causes cerebral vasodilation and reduction of the capacity of cerebral blood vessels to constrict and dilate. They also show that the glycemic thresholds for increasing cerebral blood flow are near to, or slightly lower than, the thresholds for hypoglycemic symptoms. This experimental model of hypoglycemia closely resembles the conditions in hypoglycemic patients and permits serial evaluation of the cerebrovascular effects of hypoglycemia without using anesthesia.