Granger C B
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina 27705, USA.
Am J Cardiol. 1997 Jun 19;79(12A):44-8. doi: 10.1016/s0002-9149(97)00263-4.
Although reperfusion therapy for acute myocardial infarction is known to reduce infarct size, improve left ventricular function, and reduce mortality, the full potential benefit may be limited by acceleration of damage resulting from reperfusion, or "reperfusion injury." Evidence of a variety of mechanisms of reperfusion injury has led to a wide range of proposed therapeutic interventions, including agents to prevent oxygen free radical damage, inhibit white blood cell function, reduce calcium influx, improve microvascular blood flow, inhibit sympathetic stimulation, and improve energy stores. A multitude of agents have been shown to limit infarct size in animals when administered before or during reperfusion. Unfortunately, most have been disappointing when tested clinically. Adenosine, a theoretically attractive agent for preventing reperfusion injury, has shown promise in small, clinical studies, and appears to be an endogenous substance involved in the protective effect of ischemic preconditioning. When studied in the setting of angioplasty for acute myocardial infarction, adenosine was associated with small infarct size and improved coronary flow. As myocardial preservation with reperfusion during bypass surgery shares pathophysiologic characteristics with the reperfused myocardium in acute infarction, early results of adenosine during bypass surgery presented at this symposium support the concept that adenosine may be beneficial. Two ongoing Phase II trials of adenosine in acute myocardial infarction-one with thrombolysis and one with direct angioplasty-will provide important information about the potential benefits of adenosine in the context of reperfusion.
尽管已知急性心肌梗死的再灌注治疗可缩小梗死面积、改善左心室功能并降低死亡率，但再灌注导致的损伤加速，即“再灌注损伤”，可能会限制其全部潜在益处。多种再灌注损伤机制的证据引发了一系列治疗干预措施的提议，包括预防氧自由基损伤的药物、抑制白细胞功能、减少钙内流、改善微血管血流、抑制交感神经刺激以及改善能量储备。许多药物在再灌注前或再灌注期间给药时已被证明可在动物中限制梗死面积。不幸的是，大多数药物在临床测试中都令人失望。腺苷是一种理论上有吸引力的预防再灌注损伤的药物，在小型临床研究中已显示出前景，并且似乎是参与缺血预处理保护作用的内源性物质。在急性心肌梗死血管成形术的背景下进行研究时，腺苷与较小的梗死面积和改善的冠状动脉血流相关。由于心脏搭桥手术期间再灌注时的心肌保护与急性梗死中再灌注心肌具有共同的病理生理特征，本次研讨会展示的心脏搭桥手术期间使用腺苷的早期结果支持腺苷可能有益的概念。两项正在进行的腺苷治疗急性心肌梗死的II期试验——一项联合溶栓治疗，一项联合直接血管成形术——将提供有关腺苷在再灌注情况下潜在益处的重要信息。
