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We investigated the effect of i.v. dipyridamole, a potent small-vessel coronary vasodilator, on myocardial infarct size in conscious dogs. Dipyridamole, 7-9.7 microgram/kg; 15 dogs) or saline (15 dogs) was infused for 6 hours beginning 10 minutes after acute permanent occlusion of the mid-circumflex coronary artery. After sacrifice, 48 hours after occlusion, stereoscopic postmortem angiography was used to define the mass of the occluded coronary bed. Infarct size was determined by planimetry of weighed, unstained left ventricular slices. Dipyridamole produced a striking reduction in mean infarct mass compared with control (3.1 g vs 13.2 g, p less than 0.001), while mean occluded bed mass was similar (30.3 g vs 32.7 g, NS). As a percentage of the occluded bed, mean infarct size was reduced from 36.8% to 8.6% ( p less than 0.001). Mean arterial blood pressure declined approximately 10% after dipyridamole. Heart rate and left atrial pressure did not change significantly. Collateral blood flow, measured with 8- mu radioactive microspheres, increased in all regions during dipyridamole infusion. The infarct center and border regions had sustained increases over 6 hours of 23-80%, while nonischemic regions demonstrated a diminishing response over time, with a large (98-125%) increase 10 minutes after infusion and a smaller (22-25%) increase 6 hours later. Although antiplatelet or local metabolic effects cannot be excluded, the myocardial salvage produced by dipyridamole was most likely due to the increase in collateral blood flow.