Comparative efects of nitroprusside and pinacidil on myocardial blood flow and infarct size in awake dogs with acute myocardial infarction

The effect of nitroprusside in limiting myocardial infarct was compared with that of pinacidil, a new antihypertensive agent with potent coronary vasodilator properties, in instrumented awake dogs subjected to 4 hr of left anterior descending coronary artery occlusion and 20 hr of reperfusion. Dogs were randomly assigned to receive intravenous normal saline, nitroprusside, or pinacidil beginning 40 min after the onset of coronary artery occlusion and continuing throughout the occlusion and the first hour of reperfusion. Nitroprusside and pinacidil were titrated to decrease mean aortic pressure by 25 mm Hg; normal saline had no effect on mean aortic pressure. Other systemic hemodynamic variables were not significantly altered by normal saline or nitroprusside, and myocardial blood flow did not change during normal saline infusion in normal and ischemic myocardium. In contrast, nitroprusside increased the blood flow and the endocardial/epicardial flow ratio in ischemic myocardium. This increase in ischemic myocardial blood flow was accompanied by a significant reduction in infarct size (40 3% of region at risk vs 58 + 4% in the normal saline group; p < .05). Pinacidil increased heart rate, cardiac output, and the peak rate of rise of left ventricular pressure. Furthermore, despite causing a threefold to fourfold increase in normal myocardial blood flow, pinacidil had no effect on either blood flow to ischemic myocardium or infarct size (57 5%). The data indicate that the marked coronary vasodilator effect of pinacidil does not cause an increase in ischemic blood flow or a reduction in infarct size. Instead, infarct size is reduced by nitroprusside, suggesting that the latter agent is a preferred vasodilator in acute myocardial infarction. Circulation 77, No. 3, 705-711, 1988. THE USE OF vasodilators in the treatment of patients with myocardial infarction has received considerable interest. Although the reduction in preload and afterload with the resulting decrease in myocardial oxygen consumption is a clear benefit of such agents, the decrease in coronary perfusion pressure may potentially decrease blood flow to ischemic myocardium while the reflex increase in heart rate may further exaggerate ischemic injury. Nitroprusside is a prototypical vasodilator that has been shown to improve left' ventricular function in acute myocardial infarction.' From the Cardiology Research Laboratories, Department of Medicine (Cardiology Unit), University of Rochester Medical Center, Rochester, NY. Supported in part by USPHS grant HL-30194 and by a grant from Eli Lilly and Co. Address for correspondence: Chang-seng Liang, M.D., Ph.D., Cardiology Research Laboratories, Box 679, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642. Received Oct. 22, 1987; accepted Dec. 10, 1987. Presented in part at the 60th Annual Scientific Sessions of the American Heart Association, Anaheim, CA, November 18, 1987. However, little is known regarding the elfect of nitroprusside in limiting infarct size. Nitroprusside dilates coronary arteries2 and has been shown to increase blood flow to both the normal and ischemic myocardium when it is infused to decrease arterial pressure 25 mm Hg from a hypertensive level to normal values.3 However, when arterial pressure is decreased further to 60 mm Hg below baseline with larger doses of nitroprusside in the hypertensive dogs, blood flow increases to the nonischemic myocardium and ischemic myocardial blood flow decreases.3 The latter phenomenon suggests a redistribution of coronary blood flow away from ischemic region to normal myocardium and is termed "coronary steal."4' 5 A decrease in ischemic myocardial blood flow also has been shown during infusion of nitroprusside in normotensive dogs.6 Thus the effects of nitroprusside on blood flow to ischemic myocardium may vary, depending on the doses used and the levels of blood pressure attained. Vol. 77, No. 3, March 1988 705 by gest on N ovem er 8, 2017 http://ciajournals.org/ D ow nladed from