TIME-COURSE OF CORONARY ENDOTHELIAL HEALING AFTER INJURY DUE TO ISCHEMIA AND REPERFUSION
TIME-COURSE OF CORONARY ENDOTHELIAL HEALING AFTER INJURY DUE TO ISCHEMIA AND REPERFUSION
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DOI：
10.1161/01.cir.90.5.2439
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发表时间：
1994-11-01
期刊：
影响因子：
37.8
通讯作者：
KONG, YO
中科院分区：
文献类型：
--
作者：
HORWITZ, LD;KAUFMAN, D;KONG, YO
背景尽管在短期的准备中已经证明，缺血和早期再灌注导致冠状动脉血管损伤，表现为异常的内皮依赖性舒张和血浆蛋白渗透性增加，但这些异常是永久性的还是可逆的还不清楚。方法和结果在犬模型中，通过结扎冠状动脉左前降支1小时实现局部冠状动脉缺血，并在再灌注1小时、48小时、2周或9周后进行随访研究。血管舒张测定在体外与预收缩心外膜冠状动脉环进行增加浓度的内皮依赖性血管扩张剂ADP和内皮非依赖性血管扩张剂硝普钠。在再灌注1和48小时，缺血再灌注动脉环对ADP的舒张作用减弱，但对硝普钠的舒张作用正常。在2周时，缺血/再灌注环对ADP的反应呈钝化趋势，但无显著性，在9周时观察到对ADP的反应完全正常。冠状动脉微血管通透性通过测量蛋白渗漏指数（PLI）进行评估，通过使用自体放射性标记的转铁蛋白和红细胞的双同位素技术。在再灌注1小时和48小时，在先前缺血的区域中PLI显著增加，表明血管外转铁蛋白增加。PLI在2周时略有增加，但在9周时完全正常。结论冠状动脉局部缺血1h后，冠状动脉内皮损伤在再灌注早期即已发生，心外膜冠状动脉内皮依赖性舒张功能、冠状动脉微血管通透性、微循环功能、微循环功能均出现异常，以及心外膜冠状动脉和微血管组织学。这种损伤模式持续至少48小时，但在2周内部分功能和完全组织学恢复，在9周内完全功能恢复。
Background Although it has been demonstrated in shortterm preparations that ischemia with early reperfusion results in coronary vascular injury manifested by abnormal endothelium-dependent relaxation and increased permeability to plasma proteins, it has not been clear whether these abnormalities are permanent or reversible.Methods and Results In a canine model, regional coronary ischemia was accomplished by 1 hour of left anterior descending coronary artery ligation, and follow-up studies were performed after reperfusion for 1 hour, 48 hours, 2 weeks, or 9 weeks. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside. At 1 and 48 hours of reperfusion, relaxation of rings from the ischemic reperfused artery to ADP was blunted, but relaxation to nitroprusside was normal. At 2 weeks there was a nonsignificant trend toward a blunted response to ADP in the ischemic/reperfused rings, and at 9 weeks a completely normal response to ADP was observed. Coronary microvascular permeability was assessed by measurement of protein leak index (PLI), by using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. At 1 and 48 hours of reperfusion there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. There was a small increase in PLI at 2 weeks but a completely normal measurement at 9 weeks. Electron microscopy of ischemic/reperfused vessels demonstrated endothelial cell swelling and other abnormalities in epicardial arteries and the microcirculation at 48 hours of reperfusion but normal endothelium at 2 weeks of reperfusion.Conclusions After 1 hour of regional coronary ischemia, coronary endothelial injury occurs early in reperfusion with abnormalities in epicardial coronary artery endothelium-dependent relaxation, coronary microvascular permeability, and both epicardial coronary artery and microvascular histology. This pattern of injury persists for at least 48 hours, but there is partial functional and complete histological recovery within 2 weeks and complete functional recovery within 9 weeks.