Effect of trapidil on regional myocardial function during acute coronary occlusion in the dog

The effects of an antianginal agent, N,N-diethyl-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine-7-amine (trapidil, Rocornal) (5-10 mg/kg), on regional myocardial function were studied in 17 open-chest dogs. The animals were instrumented with a micromanometer for measurement of left ventricular pressure, an electromagnetic flow probe around the left circumflex coronary artery, and 3 pairs of ultrasonic crystals in control, marginal and ischemia-induced segments. In cases of an intact coronary artery, trapidil increased peak dP/dt by 48%, heart rate by 19%, and coronary blood flow by 40%. End-diastolic segment length decreased by 7% with an increase of 17% in shortening. Coronary occlusion increased end-diastolic length of all three segments. In the ischemic segment, active shortening was rapidly replaced by systolic expansion. In the marginal segment, percent shortening decreased by 58%, while in the control segment, shortening was augmented by 11%. Trapidil administered during coronary occlusion significantly improved the shortening of control and marginal segments, as associated with a reduction in end-diastolic length. There was no significant change in function of the ischemic segment. These effects of tripidil during coronary occlusion were not blocked by propranolol (0.5-1.0 mg/kg). These data suggest that trapidil may be an effective treatment for left ventricular failure due to myocardial ischemia by virtue of its potent positive inotropic effects associated with substantial increases in myocardial blood supply sufficient to counteract the increase in oxygen consumption.