Undiminished mitochondrial function during stunning in rabbit heart at 28 degrees C.

Abstract

To investigate effect of brief ischemia on mitochondrial function in intact myocardium, rather than in isolated mitochondria. The mitochondrial response was characterized by the mean response time (tmito) of cardiac mitochondrial O2 consumption to steps in heart rate. Isolated isovolumic rabbit hearts were perfused at 28 degrees C with a constant flow of Tyrode solution containing 11 mM glucose. O2 consumption and tmito were determined before ischemia and after 25 min of no-flow global ischemia during which hearts were either paced (I + P, n = 8) or unpaced (I - P, n = 8). A non-ischemic control group (N = 8) was also examined. At 20 min reperfusion, developed left ventricular pressure (DLVP) after I + P was decreased to 47 +/- 3% (mean +/- s.e.m.; P < 0.05) of control DLVP without significant changes in venous creatine kinase efflux, indicating contractile stunning. In contrast complete contractile recovery was observed after I - P. Before ischemia, tmito was 11.2 +/- 0.6 and 14.9 +/- 0.7 s for heart rate steps from 60 to 70 and from 60 to 120 beats/min, respectively. The tmito was lower (P < 0.05) for the corresponding downward steps (10.5 +/- 0.6 and 12.4 +/- 0.6 s, respectively). An increase (P < 0.05) in tmito was observed in the course of the experiment for upward (1.2 +/- 0.3 s) and downward steps (1.4 +/- 0.3 s), but the change was similar after ischemia to that in time-matched controls (P > 0.05, both for I - P and I + P vs. control). Oxygen consumption, compared at fixed levels of the rate x pressure product, was unchanged after ischemia (P > 0.05, for both I - P and I + P vs. controls), suggesting undiminished efficiency of mitochondrial ATP production. Twenty-five minutes ischemia does not affect mitochondrial function in rabbit hearts at 28 degrees C, even when contractile stunning resulted.