Mitochondrial response to heart rate steps in isolated rabbit heart is slowed after myocardial stunning.

The oxidative capacity of mitochondria isolated from myocardium is undiminished after myocardial stunning, which is remarkable because stunning affects many other cellular functions. The aim of the present study was to assess the mitochondrial oxidative response in intact rather than isolated myocardium. The mean response time of mitochondrial O2 consumption to heart rate steps (tmito) was measured before and after 15-minute ischemia or high-flow hypoxia in isolated rabbit hearts. The tmito was calculated from the time course of venous O2 tension to steps in heart rate, with corrections made for diffusion and vascular transport delay. Isovolumic hearts were perfused with Tyrode's solution at 37 degrees C. Developed left ventricular pressure at 35 minutes of reperfusion was decreased significantly to 67 +/- 3% after ischemia (mean +/- SEM, n = 8) and to 79 +/- 6% after hypoxia (n = 8) relative to the control condition (n = 8), without increased cellular creatine kinase release. Before ischemia or hypoxia, tmito was 4.3 +/- 0.3 seconds. During reperfusion after ischemia or hypoxia, the increase in tmito (by 62 +/- 10% and 64 +/- 18%, respectively) was significantly larger than that in time controls (24 +/- 12% increase). The major determinant of decreased contractility and slower mitochondrial response appeared to be O2 deprivation and/or reintroduction rather than other consequences of stopped flow. O2 consumption at a given rate-pressure product was not increased after ischemia or hypoxia, indicating undiminished cardiac contractile economy. Brief ischemia or hypoxia, resulting in stunning, was associated with a slowing of the in vivo mitochondrial oxidative response, indicating that energy transfer and/or signaling between energy-consuming sites and mitochondria is affected in stunned myocardium.