Left ventricular unloading before reperfusion reduces endothelin-1 release and calcium overload in porcine myocardial infarction

Objectives: The aim of this Study was to test the hypothesis that after an acute myocardial infarction, endothelin-1 release with subsequent calcium overload is a mediator of myocardial reperfusion injury, which can be inhibited, in part, by left ventricular unloading immediately before reperfusion. We recently have reported that left ventricular unloading before reperfusion reduces infarct size after acute myocardial infarction. However, the biologic mechanisms of infarct salvage in unloaded hearts Subjected to ischemia/reperfusion remain undefined. Methods: Twelve pigs were subjected to I hour of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. A left ventricular assist device was initiated 15 minutes before reperfusion and maintained during reperfusion (assist device group, n = 6). A control group (n = 6) was subjected to reperfusion alone. Infarct size, endothelial-1 plasma levels, intracellular calcium levels, and apoptosis were analyzed in both groups. Results: At reperfusion, left ventricular unloading significantly decreased left ventricular end-diastolic and end-systolic pressures. Infarct size, expressed as a percentage of zone at risk, was also significantly reduced by 54% in the group with the left ventricular assist device compared with controls. Support with a left ventricular assist device reduced endothelin-1 release from the heart at 15 minutes, 30 minutes, and I hour Of reperfusion. Myocardial release of endothelin-1 was significantly con-elated with infarct size at 15 minutes of reperfusion (r = 0.79; P =.008). Left ventricular unloading caused a significant reduction of calcium overload and of the percentage of apoptotic cells in the ischemic region. Conclusion: Our findings suggest that endothelin-1 release and calcium overload are important mediators of reperfusion injury and that they can be significantly reduced by left ventricular unloading before coronary artery reperfusion during myocardial infarction.