Lactic acidosis and recovery of mitochondrial function following forebrain ischemia in the rat.
The effect of different degrees of lactic acidosis on the recovery of brain mitochondrial function, measured as respiratory activity in isolated mitochondria or cortical concentrations of labile phosphates and carbohydrate substrates, was studied during 30 min of recirculation following 15 min of near-complete forebrain ischemia in rats. During ischemia, there was a marked decrease in mitochondrial State 3 respiration in vitro and a depletion of energy stores (i.e., phosphocreatine, ATP, glucose, and glycogen) in vivo that was similar in the high- and low-lactate ischemia groups. However, lactate concentrations differed markedly (20 and 10 mumol g-1, respectively). During recirculation, there was a near-complete recovery of both respiratory activity in vitro and adenylate energy charge (EC) in vivo regardless of the differences in lactic acidosis during ischemia. Respiratory activity and EC were well correlated. The changes in Ca2+ homeostasis during ischemia, an increase in tissue and a decrease in mitochondrial Ca2+ content, were reversed rapidly after ischemia in both high- and low-lactate ischemia animals and did not hinder an early recovery of mitochondrial function. It is concluded that lactic acidosis, with lactate levels reaching 20 mumol g-1 during 15-min ischemia, does not adversely affect early postischemic recovery of mitochondrial function.
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004734:Energy Metabolism; D007773:Lactates / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration
D007773:Lactates; D002118:Calcium