MITOCHONDRIAL RESPONSE TO HEART-RATE STEPS IN ISOLATED RABBIT HEART IS SLOWED AFTER MYOCARDIAL STUNNING

The oxidative capacity of mitochondria isolated from myocardium is und iminished after myocardial stunning, which is remarkable because stunn ing affects many other cellular functions. The aim of the present stud y was to assess the mitochondrial oxidative response in intact rather than isolated myocardium. The mean response time of mitochondrial O-2 consumption to heart rate steps (t(mito)) was measured before and afte r 15-minute ischemia or high-flow hypoxia in isolated rabbit hearts. T he t(mito) was calculated from the time course of venous O-2 tension t o steps in heart rate, with corrections made for diffusion and vascula r transport delay. Isovolumic hearts were perfused with Tyrode's solut ion 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 c ontrol condition (n=8), without increased cellular creatine kinase rel ease. Before ischemia or hypoxia, t(mito) was 4.3+/-0.3 seconds. Durin g reperfusion after ischemia or hypoxia, the increase in t(mito) (by 6 2+/-10% and 64+/-18%, respectively) was significantly larger than that in time controls (24+/-12% increase). The major determinant of decrea sed contractility and slower mitochondrial response appeared to be O-2 deprivation and/or reintroduction rather than other consequences of s topped flow. O-2 consumption at a given rate-pressure product was not increased after ischemia or hypoxia, indicating undiminished cardiac c ontractile economy. Brief ischemia or hypoxia, resulting in stunning, was associated with a slowing of the in vivo mitochondrial oxidative r esponse, indicating that energy transfer and/or signaling between ener gy-consuming sites and mitochondria is affected in stunned myocardium.