Cerebral metabolic response to neonatal hypoglycemia in growth-retarded dogs.

The cerebral metabolic effects of hypoglycemia due to intrauterine growth retardation were studied in newborn dogs. Intrauterine growth retardation was induced in newborn dogs after 3 days of maternal nutritional deprivation (birth weight 251 +/- 7 versus 227 +/- 7 g, p less than 0.01). After birth, growth retarded pups developed fasting neonatal hypoglycemia which lasted from 3 to 9 h of life. The cerebral arteriovenous differences for glucose, oxygen, and ketone bodies were not different between growth-retarded pups or those from age-matched controls. The cerebral venous efflux of lactate was reduced, whereas the extraction of glucose (relative to blood glucose) was enhanced among growth-retarded pups. Cerebral glycogen content was lower in pups with growth retardation whereas phosphoenolpyruvate and pyruvate concentrations were augmented among growth-retarded pups. The latter may reflect a more oxidized cytoplasmic redox state but may also be due to diminished lactate efflux from the brain. Cerebral ATP content was not affected during periods of reduced blood glucose levels. These results suggest that in newborn dogs hypoglycemia associated with intrauterine growth retardation alters cerebral metabolism by increasing cerebral extraction of glucose and decreasing CNS efflux of lactate. We speculate that the net effect is increased lactate utilization within oxidative pathways and preservation of cerebral oxygen uptake. Cerebral glucose utilization is directed away from glycogen synthesis and toward glycolysis. Lactate oxidation rather than release to the systemic circulation may maintain cerebral ATP production in growth-retarded hypoglycemic newborn dogs.