Metabolism of the acutely ischemic dog heart. I. Construction of a computer model.

Construction of a computer model of glycolysis, the Krebs cycle, and related metabolism in acutely ischemic dog heart, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. A previous model of the same metabolism in normal-flow rat heart was modified to fit ischemic dog heart experimental data to within experimental error. The result resembles other models of ischemic heart preparations, implying common underlying mechanisms. The principal change made was reduction of enzyme amounts, consistent with the generally slower metabolism of large animals, suggesting that differing enzyme amounts are a major component of interspecies metabolic difference. Glycolytic intermediates oscillate, asynchronously and with large changes in level; pyridine nucleotides become highly reduced; pH falls, but mitochondria stay alkaline relative to cytoplasm even after oxidative phosphorylation stops.