J.M. Downey

Sustained limitation of myocardial necrosis 24 hours after coronary artery occlusion: Verapamil infusion in dogs with small myocardial infarcts

Studies were undertaken to ascertain whether verapamil infusion affords a sustained limitation of myocardial injury in the dog after a 24-hour period of coronary artery occlusion. Regional myocardial ischemia was induced by an embolization procedure which did not involve thoracotomy. Immediately after embolization radioactive microspheres were administered intraventricularly to define any area of myocardial underperfusion (zone at risk of infarction). Verapamil (0.005 mg/kg/min) was then administered and maintained for 24 hours during which time the dogs were allowed to recover from anesthesia. The control group received a corresponding infusion of saline solution. After 24 hours the dogs were killed and transverse myocardial sections (3 mm) were prepared. The resulting area of necrosis was visualized by tetrazolium staining, and risk zones were visualized by autoradiography. In the control heart, 62 +/- 7% of the zone at risk deteriorated to necrotic tissue, whereas in the verapamil-treated group only 18 +/- 4% of the tissue in the zone at risk became necrotic. Verapamil appeared to exert a significant (p less than 0.001) tissue-sparing effect that was sustained for at least 24 hours after the onset of ischemia.

Verapamil and nifedipine limit infarct size in the dog

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.