Imai N, Liang C S, Stone C K, Sakamoto S, Hood W B
Department of Medicine (Cardiology Unit), University of Rochester Medical Center, NY 14642.
Circulation. 1988 Mar;77(3):705-11. doi: 10.1161/01.cir.77.3.705.
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)
在清醒的插管犬中,将硝普钠与吡那地尔(一种具有强大冠状动脉扩张特性的新型抗高血压药物)对限制心肌梗死的作用进行了比较。这些犬接受了4小时的左前降支冠状动脉闭塞和20小时的再灌注。犬在冠状动脉闭塞开始40分钟后被随机分配接受静脉注射生理盐水、硝普钠或吡那地尔,并在整个闭塞期间和再灌注的第一个小时持续给药。硝普钠和吡那地尔进行滴定以使平均主动脉压降低25mmHg;生理盐水对平均主动脉压无影响。生理盐水或硝普钠对其他全身血流动力学变量无显著改变,在正常和缺血心肌中输注生理盐水期间心肌血流也未改变。相比之下,硝普钠增加了缺血心肌的血流以及心内膜/心外膜血流比值。缺血心肌血流的这种增加伴随着梗死面积的显著减小(危险区域的40±3%,而生理盐水组为58±4%;p<0.05)。吡那地尔增加了心率、心输出量和左心室压力的上升峰值速率。此外,尽管吡那地尔使正常心肌血流增加了三到四倍,但对缺血心肌的血流或梗死面积(57±5%)均无影响。数据表明,吡那地尔显著的冠状动脉扩张作用并未导致缺血血流增加或梗死面积减小。(摘要截短至250字)