Abstract 1105 Poster Session II, Sunday, 5/2 (poster 65)

This study was designed to determine the effect of overnight (12hr) fasting-induced mild hypoglycemia (blood glucose 50-70 mg/dl) and insulin-induced moderate hypoglycemia (blood glucose 30-40 mg/dl) on brain cell membrane function and energy metabolism during hypoxia-ischemia in newborn piglets. 62 ventilated piglets were divided into 6 groups, normoglycemic/normoxic (NN, n=8), fasting-induced mildly hypoglycemic/normoxic (FN, n=9), insulin-induced moderately hypoglycemic/normoxic (IN, n=10), normoglycemic/hypoxic-ischemic (NH, n=13), fasting-induced mildly hypoglycemic/hypoxic-ischemic (FH, n=13), and insulin-induced moderately hypoglycemic/hypoxic-ischemic (IH, n=9) group. Cerebral hypoxia-ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. Insulin-induced moderate hypoglycemia was maintained for 120 minutes before and throughout hypoxia-ischemia using modified glucose clamp technique. Blood and CSF glucose and lactate were monitored. Na++, K++-ATPase activity, lipid peroxidation products (conjugated dienes), tissue high energy phosphates (ATP and phosphocreatine) levels and brain glucose and lactate levels were determined biochemically in the cerebral cortex. During hypoxia-ischemia, glucose levels in blood and CSF were significantly lower in IH and FH group (IH < FH) than in NH group, but lactate levels in blood and CSF were not different among three groups. At the end of hypoxia-ischemia of NH, FH, and IH groups, Na+, K+-ATPase activity, ATP and phosphocreatine values in brain were significantly decreased compared with normoxic groups of NN, FN and IN, but were not different among three groups. Levels of brain lactate and conjugated dienes were significantly increased in NH, FH, and IH groups compared with NN, FN, and IN groups. Among three hypoxic groups, lactate levels were lowest in IH group, and lower in FH group than in NH group 3 (9.8 ± 3.1 vs. 13.5 ± 3.9 vs. 16.9 ± mmol/kg, p<0.05), but the levels of conjugated dienes in brain were significantly increased in hypoglycemic/hypoxic-ischemic groups (FH, IH) compared with NH group (1.19 ± 0.13, 1.17 ± 0.10 vs. 1.07 ± 0.09 mmol/g protein, p<0.05). These findings suggest that hypoglycemia does not reduce the changes in brain cell membrane function during hypoxia-ischemia in newborn piglets. We speculate that despite a lower level of brain lactate during hypoxia-ischemia than normoglycemic counterpart, hypoglycemia may be harmful during hypoxia-ischemia due to increased levels of lipid peroxidation in newborn piglets.