Lee J J, Olmos L, Vanhoutte P M
Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Proc Assoc Am Physicians. 1996 Sep;108(5):362-7.
The acute impairment of endothelium-dependent relaxations after ischemia and acute reperfusion injury has been studied extensively. However, less is known about the chronic status of the coronary endothelium following progressive reperfusion. Experiments were designed to characterize, after 60 min of ischemia followed by progressive reperfusion, the coronary endothelial function under acute and chronic conditions. Heartworm-free mongrel dogs were used. A percutaneous balloon catheter was inflated to occlude the left anterior descending coronary artery for 60 min, followed by progressive deflation. After 60 min or 4 weeks of reperfusion, the coronary arteries were dissected free, cut into rings, suspended in organ chambers, and exposed to endothelium-dependent and endothelium-independent agonists, both in the presence and absence of pertussis toxin. Left circumflex coronary arteries (from the same dogs) that had not been subjected to occlusion and reperfusion were studied in parallel as controls. The acute endothelium-dependent relaxations to serotonin, thrombin, and adenosine/diphosphate were impaired significantly following ischemia-reperfusion injury. Four weeks after ischemia-reperfusion injury, the endothelium-dependent relaxations to these substances were normal compared with those of controls. The endothelium-dependent relaxations to acetylcholine, bradykinin, and the calcium ionophore A23187 were unaffected either acutely or chronically. An early impairment of endothelium-dependent relaxations after ischemia-reperfusion injury occurs in response to serotonin, thrombin, and adenosine diphosphate. This early impairment is transient and is not evident 4 weeks after reperfusion. In contrast to the regenerated endothelium following balloon deendothelialization, the chronic endothelial pertussis toxin-sensitive G-protein function is not impaired selectively after ischemia-reperfusion injury, provided the reperfusion occurs gradually.
缺血和急性再灌注损伤后内皮依赖性舒张功能的急性损害已得到广泛研究。然而，关于渐进性再灌注后冠状动脉内皮的慢性状态，人们了解较少。本实验旨在描述在60分钟缺血后进行渐进性再灌注，急性和慢性条件下的冠状动脉内皮功能。使用无犬心丝虫的杂种犬。经皮插入球囊导管使左前降支冠状动脉闭塞60分钟，随后逐渐放气。再灌注60分钟或4周后，分离出冠状动脉，切成环状，悬挂于器官浴槽中，在有和没有百日咳毒素的情况下，分别给予内皮依赖性和非内皮依赖性激动剂。同时，对未进行闭塞和再灌注的左旋冠状动脉（来自同一只犬）作为对照进行研究。缺血再灌注损伤后，对5-羟色胺、凝血酶以及腺苷/二磷酸的急性内皮依赖性舒张功能显著受损。缺血再灌注损伤4周后，与对照组相比，对这些物质的内皮依赖性舒张功能恢复正常。对乙酰胆碱、缓激肽和钙离子载体A23187的内皮依赖性舒张功能在急性和慢性条件下均未受影响。缺血再灌注损伤后，对5-羟色胺、凝血酶和二磷酸腺苷的内皮依赖性舒张功能早期出现损害。这种早期损害是短暂的，在再灌注4周后不明显。与球囊去内皮术后再生的内皮不同，只要再灌注是逐渐发生的，缺血再灌注损伤后慢性内皮百日咳毒素敏感的G蛋白功能不会选择性受损。
