Comparative effects 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 less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)
Imai
N
N
Department of Medicine (Cardiology Unit), University of Rochester Medical Center, NY 14642.
Liang
C S
CS
Stone
C K
CK
Sakamoto
S
S
Hood
W B
WB
D000818:Animals; D003243:Consciousness; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005292:Ferricyanides / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy*; D009599:Nitroprusside / Q000627:therapeutic use*; D020110:Pinacidil; D011897:Random Allocation; D014665:Vasodilator Agents / Q000627:therapeutic use*
D005292:Ferricyanides; D006146:Guanidines; D014665:Vasodilator Agents; D009599:Nitroprusside; D020110:Pinacidil