Cerebral blood flow and metabolism during hypoglycemia in newborn dogs.
Cerebral blood flow (CBF) and cerebral metabolic rates (CMR) were studied in newborn dogs during insulin-induced hypoglycemia. Pups were anesthetized, paralyzed, and artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen to maintain normoxia and normocarbia. Experimental animals were given regular insulin (0.3 units/gm IV); controls received normal saline. CBF was determined using a modification of the Kety-Schmidt technical employing 133Xe as indicator. Arteriovenous differences for oxygen, glucose, lactate, and beta-hydroxybutyrate (beta-OHB) were also measured, and CMRO2 and CMRsubstrates calculated. Two groups of hypoglycemic dogs were identified; those in which blood glucose levels were greater than 0.5 mM (group 1), and those in which they were less than 0.5 mM (group 2). CBF did not change significantly from control values of 23 +/- 10 ml/min/100 g (mean +/- S.D.) at both levels of hypoglycemia. Similarly, hypoglycemia did not alter CMRO2 significantly from its initial level of 1.05 +/- 0.37 ml O2/min/100 g. Glucose consumption in brain during normoglycemia accounted for 95% of cerebral energy supply with minimal contributions from lactate (4%) and beta-OHB (0.5%). During hypoglycemia, CMRglucose declined by 29 and 52% in groups 1 and 2, respectively, while CMRlactate increased to the extent that this metabolite became the dominant fuel for oxidative metabolism in brain. The cerebral utilization of beta-OHB was unaltered by hypoglycemia. The findings indicate that insulin-induced hypoglycemia in the newborn dog is associated with an increase in cerebral lactate utilization, supplementing glucose as the primary energy fuel and thereby preserving a normal CMRO2. These metabolic responses may contribute to the tolerance of the immature nervous system to the known deleterious effects of hypoglycemia.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism* / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004285:Dogs; D007003:Hypoglycemia / Q000378:metabolism / Q000503:physiopathology*; D007773:Lactates / Q000097:blood; D010101:Oxygen Consumption
D001786:Blood Glucose; D007773:Lactates