Reversibility of ischemically induced mitochondrial dysfunction with reperfusion.
To clarify the reversibility of ischemically induced mitochondrial dysfunction, a murine model of hepatic ischemia was used. Following 60 minutes ischemia to one hepatic lobe, significant alterations in mitochondrial, energy-linked metabolism were apparent. After the ischemic episode, 30 minutes of reperfusion resulted in partial restoration of mitochondrial function with succinate but not alpha-ketoglutarate as substrate. Lactate accumulation was also partially reversed with reperfusion. Histologic examination subsequent to the ischemic episode revealed development of partial necrosis in nine of ten ischemic lobes. alpha-Ketoglutarate oxidation is more sensitive to injury than succinate oxidation. With proper choice of substrate, measurement of mitochondrial function just after an ischemic insult may predict subsequent hepatic failure due to cellular necrosis.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D007511:Ischemia; D007656:Ketoglutaric Acids / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008954:Models, Biological; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D051381:Rats; D013386:Succinates / Q000378:metabolism
D007656:Ketoglutaric Acids; D007773:Lactates; D013386:Succinates; D000244:Adenosine Diphosphate