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

Abstract

Objective: To investigate effect of brief ischemia on mitochondrial function in intact myocardium, rather than in isolated mitochondria.

Methods: 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.

Results: 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.

Conclusions: Twenty-five minutes ischemia does not affect mitochondrial function in rabbit hearts at 28 degrees C, even when contractile stunning resulted.