Alterations in oxidative function and respiratory regulation in the post-ischemic myocardium

S. D. Zimmer, Kamil Ugurbil, S. P. Michurski, P. Mohanakrishnan, V. K. Ulstad, John E Foker, Arthur H From

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In the normal and post-ischemic, isovolumic Langendorff perfused rat hearts, 31P NMR spectra and mechanical performance were evaluated over a wide range of myocardial oxygen consumption rates (MVO2). Hearts were perfused with either glucose and insulin, palmitate and glucose, or pyruvate and glucose and exogenous carbon sources. After ischemia at 38°C until the onset of ischemic contracture and subsequent reperfusion, the 'free' ADP levels were significantly reduced as compared to controls. In the control palmitate + glucose and glucose + insulin groups, the ADP levels were virtually independent of ~2.5-fold variation in MVO2; in contrast, they changed 4-fold with a ~30% variation in MVO2 in the post-ischemic myocardium following ischemia to contracture. In the pyruvate + glucose group, ADP levels varied with MVO2 in controls and post-ischemia; however, MVO2-ADP relationship was significantly altered following ischemia. Analysis of these observations within the concept of kinetic regulation of oxidative phosphorylation yielded the following significant conclusions: 1) the mode of respiratory regulation changed from a non-ADP to an 'ADP:P(i) limited' domain with non-pyruvate carbon sources; 2) respiratory regulation was in the ADP:P(i) limited domain before and after ischemia in the pyruvate + glucose group; however, the K(m) for the relationship between MVO2 and ADP was reduced following the ischemia/reperfusion insult; 3) the post-ischemic oxidative capacity (V(max) for MVO2) was significantly reduced in all groups and this reduction would limit maximal post-ischemic mechanical performance.

Original languageEnglish (US)
Pages (from-to)12402-12411
Number of pages10
JournalJournal of Biological Chemistry
Issue number21
StatePublished - 1989


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