Coronary thrombolysis with and without nifedipine in pigs

To investigate whether addition of Ca2+ antagonists adds to the beneficial effects of thrombolysis we studied recovery of regional myocardial performance in pigs, in which occlusive thrombi were induced by electrical stimulation, with and without addition of nifedipine to the thrombolytic agent. To this end, four different groups of animals with thrombotic coronary occlusion were studied. Groups 1 and 2 received either saline or intracoronary nifedipine (0.1 micrograms.kg-1.min-1) 15 min after coronary artery occlusion. Groups 3 and 4 were treated with the thrombolytic agent plasmin which was infused directly into the left anterior descending coronary artery (LADCA) at a rate of 2 U.min-1. The animals in group 4 also received intracoronary nifedipine. 4 h after thrombus formation the animals were sacrificed. No important differences in systemic hemodynamics were observed between the four groups of animals. Reperfusion occurred only in the animals which received plasmin, with or without nifedipine. After intracoronary plasmin regional blood flow increased from 7 +/- 2 to 40 +/- 7 ml.min-1.100 g-1 in the LADCA-perfused subepicardial and from 9 +/- 2 to 30 +/- 6 ml.min-1.100 g-1 in the LADCA-perfused subendocardial layers. The combination of plasmin and nifedipine increased flow to the LADCA-perfused subepicardial layers from 8 +/- 2 to 74 +/- 21 ml.min-1.100 g-1 and that to the subendocardial layers from 8 +/- 2 to 57 +/- 16 ml.min-1.100 g-1 (in both cases: p less than 0.05 vs. plasmin alone). However, addition of nifedipine did not enhance recovery of regional myocardial function or high-energy phosphate metabolism. Because reperfusion was accompanied by a high ventricular ectopic activity, the question may be raised of whether reperfusion of ischemic myocardium which does not result in functional recovery could be deleterious.