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

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.