Cerebral Blood Flow and Metabolism During Hypoglycemia in Newborn Dogs

Abstract

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.

Substrate Utilization and Brain Development

“…Gregoire et al (1978) found a mean CBF of 48 ml 100 g-l min-l and a cerebral metabolic rate for glucose (CMRg1u) of 20 /Lmol 100 g-l min-1 in fed puppies (Table 2). Glucose cerebral extraction was higher in the studies of Weng et al (1973) and lower in those of Hernandez et al (1980).…”

“…The influence of insulin-induced hypoglycemia on CBF and metabolic rate in newborn puppies was studied by Hernandez et al (1980). Mean values for CBF were the same in hypoglycemic animals as in normoglycemic animals at 26 ml 100 g-l min-I.…”

Hepatic and Cerebral Energy Metabolism after Neonatal Canine Alimentation

“…There is a paucity of data that describes the effects of alimentation on cerebral cortical glycolytic intermediates among adults or neonates. It is known however that fetal and neonatal cerebral glucose uptake is related to circulating glucose levels (19,28). It was therefore possible that increased provision of glucose to the brain and subsequent enhanced cerebral glucose utilization and glycolysis had resulted in the intermediate alterations reported here.…”

Cerebral Metabolic Intermediate Response following Severe Canine Intrauterine Growth Retardation

“…Lactate may function as cerebral cortical fuel in many newborn species, including man (14)(15)(16). Other studies among newborn beagles by our group (1 8) and Gregoire et al (17) have demonstrated release of lactate from the brain.…”

“…In adult rats with mild to moderate hypoglycemia, cerebral energy metabolism may be unaltered as ATP levels do not decline (20). Furthermore cerebral oxygen consumption is not reduced in hypoglycemic dogs despite a marked decline in the total cerebral utilization of glucose (15). It has been hypothesized that augmented oxidation of endogenous cerebral substrates maintains the energy status of the brain.…”