Kloner R A, Ganote C E, Jennings R B
J Clin Invest. 1974 Dec;54(6):1496-508. doi: 10.1172/JCI107898.
The role of microvascular damage in the genesis of the "no-reflow" phenomenon was investigated in the left ventricular myocardium of dogs subjected to temporary occlusions of a major coronary artery for 40 and 90 min. Intravenous carbon black or thioflavin S (a fluorescent vital stain for endothelium) were used to demonstrate the distribution of coronary arterial flow in control and damaged myocardium. These tracers were injected simultaneously with release of the coronary occlusion or after 5 or 20 min of reflow of coronary arterial blood. After 40 min of ischemia plus arterial reperfusion, usually the tracers were evenly distributed throughout the damaged tissue at each time of reperfusion. On the other hand, when reflow was allowed after 90 min of ischemia, portions of the inner half of damaged myocardium were not penetrated by the tracers. Electron microscopic study of this poorly perfused tissue revealed severe capillary damage; endothelial cells with large intraluminal protrusions and decreased pinocytic vesicles were common. Also, occasional intraluminal fibrin thrombi were noted, as well as extravascular fibrin deposits and erythrocytes. Myocardial cells were swollen in both poorly perfused and well-perfused irreversibly injured tissue. Contraction bands and mitochondrial Ca(2+) accumulation were prominent features of irreversible injury with reflow at 40 min but were not noted after 90 min of ischemia in areas with poor perfusion. These results suggest that 40 min of ischemia were tolerated by the capillary bed of the dog heart without serious capillary damage or perfusion defects, but that 90 min of ischemic injury was associated with the "no-reflow" phenomenon, i.e., failure to achieve uniform reperfusion. This failure of reflow was associated with extensive capillary damage and myocardial cell swelling. Death of severely ischemic myocardial cells in this model occurs before the onset of capillary damage and the no-reflow phenomenon.
在经历主要冠状动脉临时闭塞40分钟和90分钟的犬左心室心肌中，研究了微血管损伤在“无复流”现象发生中的作用。静脉注射炭黑或硫黄素S（一种内皮细胞荧光活体染料），以显示对照心肌和受损心肌中冠状动脉血流的分布。这些示踪剂在冠状动脉闭塞解除时或冠状动脉血液再灌注5分钟或20分钟后同时注射。缺血40分钟加动脉再灌注后，通常在每次再灌注时示踪剂均匀分布于整个受损组织。另一方面，当缺血90分钟后再灌注时，受损心肌内半部分的一些区域未被示踪剂穿透。对这种灌注不良组织的电子显微镜研究显示严重的毛细血管损伤；内皮细胞内有大的腔内突起且胞饮小泡减少很常见。此外，偶尔可见腔内纤维蛋白血栓以及血管外纤维蛋白沉积和红细胞。在灌注不良和灌注良好的不可逆损伤组织中，心肌细胞均肿胀。收缩带和线粒体Ca(2+)积累是40分钟再灌注时不可逆损伤的突出特征，但在灌注不良区域缺血90分钟后未观察到。这些结果表明，犬心脏的毛细血管床能够耐受40分钟的缺血，而无严重的毛细血管损伤或灌注缺陷，但90分钟的缺血性损伤与“无复流”现象相关，即未能实现均匀再灌注。这种复流失败与广泛的毛细血管损伤和心肌细胞肿胀有关。在该模型中，严重缺血心肌细胞的死亡发生在毛细血管损伤和无复流现象出现之前。
