Ischemic damage is greatly enhanced by preischemic
hyperglycemia or
hypercapnia, which affects many intracellular responses including
protein kinase C (PKC) translocation. We explored whether hyperglycemic or hypercapnic
ischemia affects lipid metabolism, especially
ischemia-induced release of
free fatty acids (FFAs) and
diacylglycerols (DAGs). A change in intraischemic level of
acidosis was induced either by injecting
glucose (hyperglycemic, HG) or by adding CO(2) (hypercapnic, HC). Complete
cerebral ischemia was induced, and the brain was frozen in situ after 3, 5, and 10 min at 37 degrees C. Frontoparietal neocortex was dissected for FFA and DAG
lipid analysis by thin-layer chromatography and gas-liquid chromatography. Significant differences were shown between normoglycemic and either hypercapnic or hyperglycemic values for individual and total FFAs. A significant delay in the release of FFA in
ischemia with
hyperglycemia or
hypercapnia was observed. Significant differences were also shown in individual DAG-acyl groups and total DAGs. Hyperglycemic or hypercapnic
ischemia resulted in a significant decrease of DAG
at 10 min of
ischemia. This was unexpected because a previous study showed that PKC translocation was significantly enhanced under similar condition at this time point. Upon cellular depolarization, massive influx of
calcium and FFA accumulation may decrease the PKC dependence of DAG for translocation. In addition, PKC activation may lead to a negative feedback inhibition of
phospholipase C.