Pelc L R, Garancis J C, Gross G J, Warltier D C
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Circulation. 1990 Jun;81(6):1928-37. doi: 10.1161/01.cir.81.6.1928.
We have previously demonstrated that intracoronary infusion of the endothelium-dependent vasodilators acetylcholine, ATP, or arachidonic acid produces a preferential increase in subendocardial blood flow in anesthetized dogs. This study was performed to assess the effects of coronary artery occlusion and reperfusion on the distribution of myocardial blood flow produced by endothelium-dependent and endothelium-independent vasodilators. The endothelium was damaged by occlusion of the left anterior descending coronary artery for 45 minutes followed by 60 minutes of reperfusion in pentobarbital-anesthetized dogs. Intracoronary infusions of the endothelium-dependent vasodilators acetylcholine, bradykinin and thiazolylethylamine or the endothelium-independent vasodilator sodium nitroprusside were performed, and regional myocardial blood flow (by radioactive microspheres) was measured before and after occlusion and reperfusion. There were no changes in systemic hemodynamics during intracoronary infusion of vasodilators before or after coronary occlusion and reperfusion. All vasodilators produced similar increases in transmural blood flow before occlusion; however, only the endothelium-dependent vasodilators produced a significant increase in the subendocardial-to-subepicardial blood flow ratio. Increases in transmural flow as well as the preferential increase in subendocardial blood flow produced by acetylcholine, bradykinin, and thiazolylethylamine were attenuated after coronary occlusion and reperfusion. In contrast, increases in transmural blood flow produced by sodium nitroprusside were unchanged. These results suggest that the preferential increase in subendocardial perfusion produced by acetylcholine, bradykinin, and thiazolylethylamine is endothelium-dependent and may be selectively modified by ischemic insult.
我们之前已经证明，在麻醉犬体内冠状动脉内输注内皮依赖性血管舒张剂乙酰胆碱、ATP或花生四烯酸会使心内膜下血流优先增加。本研究旨在评估冠状动脉闭塞和再灌注对内皮依赖性和非内皮依赖性血管舒张剂所产生的心肌血流分布的影响。在戊巴比妥麻醉的犬中，通过闭塞左前降支冠状动脉45分钟，随后再灌注60分钟来损伤内皮。进行冠状动脉内输注内皮依赖性血管舒张剂乙酰胆碱、缓激肽和噻唑基乙胺或非内皮依赖性血管舒张剂硝普钠，并在闭塞和再灌注前后测量局部心肌血流（通过放射性微球）。在冠状动脉闭塞和再灌注前后进行冠状动脉内输注血管舒张剂期间，全身血流动力学没有变化。在闭塞前，所有血管舒张剂均使透壁血流产生相似的增加；然而，只有内皮依赖性血管舒张剂使心内膜下与心外膜下血流比值显著增加。冠状动脉闭塞和再灌注后，乙酰胆碱、缓激肽和噻唑基乙胺所产生的透壁血流增加以及心内膜下血流的优先增加均减弱。相比之下，硝普钠所产生的透壁血流增加没有变化。这些结果表明，乙酰胆碱、缓激肽和噻唑基乙胺所产生的心内膜下灌注优先增加是内皮依赖性的，并且可能会被缺血性损伤选择性地改变。
