Maturational changes in cerebral lactate and acid clearance following ischemia measured in vivo using magnetic resonance spectroscopy and microdialysis

Intraischemic hyperglycemia has different effects on neurologic outcome in mature vs. immature brain, and may reflect differences in the extent or dur ation of cerebral lactic acidosis. We examined the hypotheses that post-isc hemic lactate and acid clearance rates depend on the severity of intraische mic cerebral acidosis, and that rates of clearance change as a function of brain maturation. In vivo P-31 and H-1 magnetic resonance spectroscopy (MRS ) was used to compare intracellular acid and lactate clearance rates in new born and 1-month old swine following a 14-min episode of transient near-com plete global ischemia. In the same animals, in vivo microdialysis was used to determine if extracellular lactate clearance changed as a function of ce rebral lactic acidosis or differed between age groups following ischemia. P lasma glucose concentration was altered in individual animals to study a ra nge of intraischemic cerebral lactic acidosis. For both age-groups, maximal brain acidosis and lactosis occurred in the post-ischemia interval, indica ting a delay in the re-establishment of oxidative metabolism following isch emia. Clearance half-lives of both cerebral acidosis and lactosis increase as a function of increased intraischemic cerebral acidosis. For either age group, the clearance half-life for acidosis was faster than the half-life f or lactate. However, the subgroup of 1-month old swine who experienced seve re cerebral acidosis (i.e., pH < 6.1) had a longer cerebral lactate clearan ce half-life as compared to the subgroup of newborn animals with a similar severity of acidosis. In both age groups, there were comparable maximal inc reases in extracellular lactate concentrations in the post-ischemic period and similar rates of decline from the maximum. These results demonstrate th at post-ischemic lactate and acid clearance are altered by the extent of in traischemic acidosis, and the extent of post-ischemic uncoupling between br ain acid and lactate clearance increases with advancing age. The transmembr ane clearance of lactate was not a prominent mechanism that differentiated lactate clearance rates between newborn and 1-month old swine. (C) 1999 Els evier Science B.V. All rights reserved.