Kelly R F, Hursey T L, Schaer G L, Piotrowski M J, Dee S V, Parrillo J E, Hollenberg S M
Section of Cardiology, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
J Investig Med. 1996 Dec;44(9):575-82.
The potent vasoconstrictor endothelin-1 (ET) may play an important pathophysiologic role in acute myocardial infarction, but its precise effects are incompletely understood. The purpose of this study was to evaluate the interrelationships between cardiac ET-1 release and infarct size, myocardial blood flow, and ventricular function.
Fifteen closed chest dogs underwent 3 hours of coronary artery occlusion followed by 3 hours of reperfusion. Coronary sinus and aortic ET-1 levels during occlusion and after reperfusion were determined by radioimmunoassay. Left ventricular function and regional myocardial blood flow were measured by echocardiography and colored microspheres, respectively. Myocardial infarct size was determined by postmortem staining with blue dye and triphenyl tetrazolium chloride.
Coronary occlusion and reperfusion produced significant elevations of coronary sinus ET-1 (p < 0.05) and cardiac ET-1 release (p < 0.05), and a trend toward an increase in aortic ET-1 (p = 0.08). A trend toward more ET-1 release was observed in dogs with larger infarcts (p = 0.06), and in dogs with substantial no-reflow in the reperfused territory (p = 0.05). Endothelin-1 release also was associated with increased contractility in nonischemic myocardial segments (p = 0.002), and ET-1 correlated with increased global left ventricular function (p < 0.02).
In this canine model of coronary occlusion and reperfusion, greater increases in cardiac ET-1 release were observed in dogs with larger infarcts, and increased ET-1 release was associated with the no-reflow phenomenon in the reperfused territory. These data suggest that ET-1 release may have adverse consequences in acute myocardial infarction, including a reduction of myocardial blood flow in the reperfused zone after reperfusion and increased contractility in nonischemic myocardium.
强效血管收缩剂内皮素-1（ET）可能在急性心肌梗死中发挥重要的病理生理作用，但其确切作用尚未完全明确。本研究旨在评估心脏ET-1释放与梗死面积、心肌血流及心室功能之间的相互关系。
15只开胸犬接受3小时冠状动脉闭塞，随后再灌注3小时。通过放射免疫分析法测定闭塞期间及再灌注后冠状窦和主动脉ET-1水平。分别采用超声心动图和彩色微球测量左心室功能和局部心肌血流。通过死后用蓝色染料和氯化三苯基四氮唑染色确定心肌梗死面积。
冠状动脉闭塞和再灌注导致冠状窦ET-1（p<0.05）和心脏ET-1释放显著升高（p<0.05），主动脉ET-1有升高趋势（p=0.08）。在梗死面积较大的犬（p=0.06）和再灌注区域有大量无复流的犬（p=0.05）中观察到ET-1释放有增加趋势。内皮素-1释放还与非缺血心肌节段收缩力增加有关（p=0.002），且ET-1与整体左心室功能增加相关（p<0.02）。
在这个冠状动脉闭塞和再灌注的犬模型中，梗死面积较大的犬心脏ET-1释放增加更明显，且ET-1释放增加与再灌注区域的无复流现象有关。这些数据表明，ET-1释放在急性心肌梗死中可能产生不良后果，包括再灌注后再灌注区心肌血流减少以及非缺血心肌收缩力增加。
