title: Influence of cerebral ischemia and post-ischemic reperfusion on mitochondrial oxidative phosphorylation.
abstract: Unilateral ischemia in the right cerebral hemisphere of the rat was induced by ligation of the right common carotid artery coupled with controlled hemorrhage to produce hypotension (25 +/- 8 mm/Hg). Where indicated after 30 min of ischemia, the withdrawn blood was reinfused to restore arterial pressure to normal. Mitochondria isolated from the ipsilateral hemisphere after 30 min of ischemia showed significantly lower respiratory rates than the organelles isolated from the contralateral side. Oxidation of NAD(+)-linked substrates was more sensitive to inhibition in ischemia (30%) than was of ferrocytochrome c (12%), succinate oxidation being intermediate. The activities of membrane-bound dehydrogenases (both NADH and succinate-linked) were also significantly lowered. Ischemia did not affect the cytochrome content of mitochondria. Respiratory activity (NAD(+)-linked) of mitochondria isolated from the ipsilateral hemisphere was twice as sensitive to inhibition by fatty acid as was of preparations from the contralateral side. Mitochondria isolated from cerebral cortex after 90 min of post-ischemic reperfusion showed no significant improvement in the rate of substrate oxidation. Adenine nucleotide translocase activity and energy-dependent Ca2+ uptake, both of which decreased significantly in mitochondria isolated from the ischemic brain, showed little recovery, on reperfusion. These observations suggested the strong possibility that the deleterious effects of ischemia on mitochondrial respiratory function might be mediated by free fatty acids that are known to accumulate in large amounts in ischemic tissues. The pattern of inhibition of ATPase activity was consistent with this view.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, India.
authors.forename: C K
authors.initials: CK
authors.lastname: Kurup
authors.forename: K K
authors.initials: KK
authors.lastname: Kumaroo
authors.forename: A J
authors.initials: AJ
authors.lastname: Dutka
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002545:Brain Ischemia / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D005227:Fatty Acids / Q000378:metabolism; D005362:Ficoll; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D005362:Ficoll