AJP - Regulatory, Integrative and Comparative Physiology, Vol 240, Issue 3 192-R199, Copyright © 1981 by American Physiological Society
Cerebral carbohydrate and energy metabolism during hypoglycemia in newborn dogs
R. C. Vannucci, E. E. Nardis, S. J. Vannucci and P. A. Campbell
The metabolic responses of the perinatal brain to hypoglycemia were studied
in newborn dogs. Hypoglycemia, induced by the intravenous injection of
regular insulin (0.2-0.3 U/g body wt), resulted in final blood glucose
concentrations ranging from 0.1 to 1.5 mmol/l; blood lactate levels were
little changed from normoglycemic values. Righting, sucking, and
nociceptive withdrawal reflexes were progressively lost during the course
of hypoglycemia. Slowing of the electroencephalogram was apparent at or
below 1.5 mmol/l blood glucose and advanced to paroxysmal discharges and
convulsive activity as glucose approached 0.5 mmol/l. In lightly
anesthetized, paralyzed, and artificially ventilated puppies, blood glucose
concentrations approximating 1.0 mmol/l were associated with a 91%
reduction in cerebral glucose; the concentrations of other glycolytic
intermediates (glucose 6-phosphate, fructose 6-phosphate, fructose
1,6-diphosphate, pyruvate, lactate) were unchanged from control. Further
declines in blood glucose resulted in cerebral glucose levels below 0.1
mmol/kg as well as in partial depletions of all measured glycolytic
intermediates including lactate. These changes reflect reduced cerebral
glucose consumption and glycolytic flux. Despite the alterations in
carbohydrate metabolism, both lactate/pyruvate ratios and high-energy
phosphate reserves (phosphocreatine, ATP, ADP) in brain were well preserved
even at the extreme of hypoglycemia. The present data, coupled with
previous findings of enhanced lactic acid entry into and consumption by
newborn dog brain, suggest that this metabolite serves as an important, if
not the predominant, substitute fuel for cerebral oxidative metabolism
during perinatal hypoglycemia.
