Protective Effect of Early and Late Treatment with Nifedipine During Myocardial Infarction in the Conscious Dog

The effect of early and late nifedipine treatment on collateral blood flow and myocardial infarct size was investigated in 24 previously instrumented conscious dogs. Nifedipine was infused intravenously for 5 hr beginning 15 min (n = 9) and 3 hr (n = 6) after permanent occlusion of the midcircumflex coronary artery and compared with early and delayed vehicle treatment (controls; n = 9). Doses of nifedipine (90 to 168 micrograms/hr) were titrated to reduce mean arterial pressure by 5% to 10%. After animals died or were killed 2 to 7 days later, the anatomic risk region, or occluded coronary bed, was defined by postmortem coronary arteriography. The masses of infarct and risk region were measured by planimetry of weighed transverse sections of the left ventricle. Infarct size was smaller (p less than .05) with early and late nifedipine treatment compared with control, both as percent of left ventricle (15.6% and 14.6% vs 21.6%) and as percent of risk region (46.7% and 41.6% vs 65.7%). Collateral blood flow, measured with radioactive microspheres, increased 31% to 50% during 5 hr of nifedipine treatment, but the mean increase was not statistically greater than that seen in controls. Myocardial protection by nifedipine occurred consistently when epicardial collateral flow exceeded 0.40 ml/min/g and the increase after the drug was at least 0.1 ml/min/g. When flows were less than these amounts, however, only about half of the animals demonstrated reduced infarct size. The results suggest that an increase in collateral flow accounts for part of the beneficial effect of nifedipine but that direct mechanisms not mediated by flow may also contribute.