Failure to Demonstrate Myocardial Protective Effects of the Ultra Short-Acting Calcium Antagonist Clevidipine in a Closed-Chest Reperfusion Porcine Model

Restoration of myocardial perfusion is essential in acute myocardial infarction for the salvaging of myocardial tissue. However, reperfusion per se can provoke myocardial necrosis within the jeopardized tissue. Yet, no intervention has been successfully applied to the clinical situation in this matter. Clevidipine, an ultra-short acting calcium antagonist, has, in open-chest animal models, shown to reduce the extent of reperfusion injury. In the present study we intended to reproduce those findings in a closed-chest porcine model with a clinically applicable set up. Pigs were subjected to balloon occlusion of the left anterior descending coronary artery (LAD) for 45 minutes. During 25 minutes, starting 1 minute prior to reperfusion, clevidipine, Intralipid, or saline was infused antegradely into the endangered myocardium. As no significant effects on infarct size were achieved, the model was modified. In a second phase, different anesthesias were evaluated addressing the same issue. Nonetheless no significant effects on infarct size were observed. Different techniques of occluding LAD, in an open-chest model, were investigated in a third phase, and revealed no significant differences between the techniques. However, when comparing all the closed- versus open-chest models, significant reduction in infarct size by the use of clevidipine was only obtained in the open-chest models. We could not demonstrate any significant myocardial protective effect with clevidipine in our porcine, closed-chest, acute infarct, and reperfusion model. However, in a modified open-chest model we obtained significant reduction in infarct size. Further studies are required to explain the discrepancies.