Hypoglycemia prevents increase in lactic acidosis during reperfusion after temporary cerebral ischemia in rats

Abstract

Sequential 31P and 1H MRS was used to measure cerebral phosphate metabolites, intracellular pH, and lactate in normoglycemic and hypoglycemic rats during 30 min of complete cerebral ischemia and 5.5 h of reperfusion. These results were correlated with brain levels of free fatty acids (FFAs), excitatory amino acids, cations, and water content at death. The lactate/N-acetyl aspartate ratio was not significantly different between groups before or during occlusion. During reperfusion, the ratio was higher in normoglycemic rats from 3 to 85 min (p < or = 0.05), and recovery time was faster in hypoglycemic rats (29 vs 45 min; p = 0.04), suggesting reduced lactate production and faster recovery of aerobic metabolism. During occlusion, significant but comparable decrease of intracellular pH occurred in each group. Intracellular pH was higher in hypoglycemic rats at 140 min and 260 min of reperfusion. Water content, Na and K+ concentrations, and FFA and excitatory amino acid levels were not significantly different between groups, but hypoglycemic rats had less depletion of levels of Mg2+ (p = 0.011). These results show that hypoglycemia has a limited but potentially beneficial effect on postischemic lactic acidosis.

Figure 1

Time course of changes in serum glucose levels (mean ± SE) in seven normoglycemic and seven hypoglycemic rats. Insulin induced a significant decrease in glucose (112.5 ± 6.4 to 34.9 ± 4.6 mg/dL; _p = 0.0003) 5 min before occlusion in the hypoglycemia group. Serum glucose increased nearly to physiologic levels (85.4 ± 8.6 mg/dL) in the hypoglycemic group by 220 min of reperfusion.

Figure 2

(a) Normal baseline proton brain spectrum (lower right) and stacked ¹H edited spectra obtained sequentially in a normoglycemic rat during 30 min complete global cerebral ischemia and 5.5 h reperfusion are presented. Note increase in size of lactate peak during occlusion with additional increase followed by gradual recovery during reperfusion. (b) Sequential ³¹P spectra from the same rat demonstrate temporary PCr and ATP depletion and P_i increase during 30 min of global ischemia.

Figure 3

(a) Time course of changes in MRS peak areas for ATP, PCr and P_i (mean ± SD) during temporary ischemia n normoglycemic and hypoglycemic rats. All data inparts per million normalized to preischemic values of 1.0. There were no significant differences between the groups.

Figure 3

(b) Time course of changes in intracellular pH (pH_i) (mean ± SD) measured by ³¹P MRS in normoglycemic and hypoglycemic rats. The difference between groups during ischemia is not statistically significant. However, pH_i recovered to preischemic levels more rapidly (35 vs 75 min of reperfusion; p<0.05) in hypoglycemic than in normoglycemic rats. pH was slightly but significantly higher only at 140 and 260 min of reperfusion (p = 0.011 and 0.014, respectively) in hypoglycemic rats than in normoglycemic rats.

Figure 4

Time course of lactate/NAA ratios (mean ± SE) in seven normoglycemic and seven hypoglycemic rats. The lactate/NAA ratio was significantly lower (p≤0.05) in the hypoglycemia group from 3 to 85 min of reperfusion, and again at 240 min reperfusion.