Mitochondrial response to transient forebrain ischemia and recirculation in the rat.

Recovery of brain mitochondrial function was studied following forebrain ischemia induced in rats by common carotid artery occlusion in combination with hypotension caused by bleeding. A reversible insult was induced by 15-min ischemia in fasted animals (hypoglycemic ischemia), and an irreversible one by 30-min ischemia in fed animals (normoglycemic ischemia), the latter procedure causing exaggerated lactic acidosis as well. Mitochondrial function recovered during a 30-min recirculation period after 15-min hypoglycemic ischemia, although a small amount of Ca2+ accumulated during recirculation. Thirty-minute normoglycemic ischemia induced irreversible mitochondrial damage that was not associated with Ca2+ accumulation during recirculation. Ischemia of 15 and 30 min caused a loss of mitochondrial Mg2+ (approximately 25%) that persisted during recirculation but did not influence recovery. Based on our earlier data obtained on isolated brain mitochondria in vitro, it is suggested that the lack of full recovery following 30 min of normoglycemic ischemia was due to the profound lactic acidosis during this insult.