Verapamil and nifedipine limit infarct size in the dog

Abstract

We studied the ability of two calcium antagonists, nifedipine and verapamil, to limit infarct size in the closed-chest, coronary-embolized dog. Immediately after embolization, 141Ce-labeled microspheres were administered into the left ventricle. Myocardium not receiving microspheres was considered to be the region at risk. The nifedipine group received 16 micrograms/kg, i.v., over 8 min as a loading dose, followed by continuous infusion (0.04 mg/kg per 24 hr) within 10 min after embolization. The verapamil group received a 0.2 mg/kg bolus over 2 min, followed by a continuous infusion of 8 mg/kg per 24 hr. Again, the drug was started within 10 min of embolization. The control groups received an equal volume of saline. At 24 hr after embolization, the dogs were sacrificed, the hearts were sectioned into 3-mm slices, and the slices were stained with tetrazolium to reveal the infarct. The region at risk was determined by autoradiography of the microspheres in the heart slices. Infarct and risk-zone volume were determined by planimetric methods. Infarct size was normalized by expressing it as a percentage of the region at risk. Nifedipine significantly reduced this percentage when compared to matched controls (38.7 +/- 4.7 vs. 79.5 +/- 4.3%, p less than 0.001). Similarly, verapamil also reduced infarct size (18.0 +/- 4.4 vs. 62.0 +/- 7.4%, p less than 0.001). We conclude that both these drugs appear to offer protection in the presence of permanent coronary occlusion.