Farb A, Kolodgie F D, Jenkins M, Virmani R
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000.
J Am Coll Cardiol. 1993 Apr;21(5):1245-53. doi: 10.1016/0735-1097(93)90253-w.
The goal of this study was to demonstrate myocardial infarct extension during reperfusion within the same animal.
Whether myocardial reperfusion can result in the extension of myocardial necrosis remains controversial. The transformation of reversibly injured myocytes into irreversibly damaged cells after reperfusion has been difficult to demonstrate pathologically.
New Zealand White rabbits (Group I, n = 10) were subjected to 30 min of coronary artery occlusion and 180 min of reperfusion. Horseradish peroxidase, a tracer protein that permeates the sarcolemma of irreversibly injured myocytes, was used to quantitate myocyte necrosis at the beginning of reperfusion. Within the same heart, infarct size was measured after 180 min of reperfusion by triphenyltetrazolium chloride (TTC) staining. In separate experiments to demonstrate the validity of the model, rabbits were subjected to 30 min of coronary occlusion, followed by intravenous infusion of horseradish peroxidase and rapid induction of death (Group II) or 30 min of occlusion, 180 min of reperfusion with horseradish peroxidase administered after 180 min of reperfusion and TTC staining after induced death (Group III).
In Group I, infarct size at the onset of reperfusion, delineated by horseradish peroxidase, measured 45.3 +/- 2.8% of the area of risk and was significantly less than TTC-delineated infarct size after 180 min of reperfusion (59.8 +/- 3.3%, p = 0.0002). By electron microscopy, border areas within the ischemic bed demonstrated irreversibly injured horseradish peroxidase-positive myocytes adjacent to irreversibly injured horseradish peroxidase-negative myocytes, suggesting that further cell death occurred during reperfusion. In Group II, infarcts delineated by horseradish peroxidase after 30 min of coronary occlusion were similar in size to infarcts measured by this tracer in Group I. In Group III, infarcts delineated by horseradish peroxidase at 180 min of reperfusion were similar in size to infarcts measured by TTC and similar to TTC-delineated infarcts measured at 180 min of reperfusion in Group I.
These results provide evidence that there is a subset of myocytes in border areas within the ischemic region that are viable at the beginning of reperfusion but subsequently progress to irreversible injury during the reperfusion period.
本研究的目的是在同一只动物体内证明再灌注期间心肌梗死范围的扩大。
心肌再灌注是否会导致心肌坏死范围扩大仍存在争议。再灌注后可逆性损伤的心肌细胞转变为不可逆性损伤细胞，这在病理学上难以证实。
将新西兰白兔（第一组，n = 10）冠状动脉闭塞30分钟，再灌注180分钟。辣根过氧化物酶是一种可渗透不可逆性损伤心肌细胞肌膜的示踪蛋白，用于在再灌注开始时定量心肌细胞坏死情况。在同一心脏内，再灌注180分钟后通过氯化三苯基四氮唑（TTC）染色测量梗死面积。在单独的实验中为证明该模型的有效性，将兔子冠状动脉闭塞30分钟，随后静脉注射辣根过氧化物酶并快速诱导死亡（第二组），或闭塞30分钟，再灌注180分钟，在再灌注180分钟后注射辣根过氧化物酶并在诱导死亡后进行TTC染色（第三组）。
在第一组中，由辣根过氧化物酶界定的再灌注开始时的梗死面积为危险区域面积的45.3±2.8%，显著小于再灌注180分钟后TTC界定的梗死面积（59.8±3.3%，p = 0.0002）。通过电子显微镜观察，缺血区域内的边界区域显示，不可逆性损伤的辣根过氧化物酶阳性心肌细胞与不可逆性损伤的辣根过氧化物酶阴性心肌细胞相邻，提示再灌注期间发生了进一步的细胞死亡。在第二组中，冠状动脉闭塞30分钟后由辣根过氧化物酶界定的梗死面积与第一组中用该示踪剂测量的梗死面积相似。在第三组中，再灌注180分钟时由辣根过氧化物酶界定的梗死面积与TTC测量的梗死面积相似，且与第一组中再灌注180分钟时TTC界定的梗死面积相似。
这些结果提供了证据，表明在缺血区域边界区域存在一部分心肌细胞，它们在再灌注开始时是存活的，但在再灌注期间随后进展为不可逆性损伤。
