Leukocyte adhesion to the coronary microvasculature during ischemia and reperfusion in an in vivo canine model
Leukocyte adhesion to the coronary microvasculature during ischemia and reperfusion in an in vivo canine model
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DOI：
10.1161/01.cir.93.10.1784
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发表时间：
1996-05-15
期刊：
影响因子：
37.8
通讯作者：
Ramage, D
中科院分区：
文献类型：
--
作者：
Sheridan, FM;Cole, PG;Ramage, D
背景：缺血心肌或处于梗死过程中的心肌的迅速再通是目前冠心病治疗的基石。矛盾的是，实验证据表明，心脏损伤可能是由再灌流本身造成的。白细胞在再灌流过程中附着于冠脉血管内皮细胞可能是这一有害过程的起始步骤。在心脏缺血和再灌流模型中，白细胞与微血管内皮细胞的黏附从未被直接证明。方法和结果在开胸犬的左心室表面，通过一种特殊的“浮动”物镜，允许一系列晶状体与跳动的狗心脏同步运动，使用了荧光视频显微镜。心外膜微血管(25~130微米)在缺血1小时、再灌流2小时、缺血3小时或无缺血3小时期间，注入吖啶橙(荧光标记白细胞)后记录。代表白细胞聚集的微血管壁上记录的净荧光量在再灌流期间(n=8)与保持缺血的动物(n=5)相比显著增加(21.0+/-3.8比10.9+/-4.5灰度级；P=0.0001)。在同一组动物中，再灌流期间荧光的快速增加也与前一次缺血时显著不同(21.0+/-3.8对5.1+/-2.1灰阶；P=0.0001)，而在整个实验过程中保持缺血的动物在同一时间段内未见明显增加。结论与单纯缺血相比，再灌流促进了白细胞在冠脉微血管中的快速聚集。
Background Prompt reperfusion of ischemic myocardium or myocardium that is in the process of becoming infarcted is a cornerstone of current therapy for coronary artery disease. Paradoxically, experimental evidence suggests that cardiac damage may be caused by the reperfusion itself. Leukocyte attachment to the coronary vascular endothelium during reperfusion may be an initiating step in this detrimental process. Leukocyte adhesion to microvascular endothelium has never been demonstrated directly in a cardiac model of ischemia and reperfusion.Methods and Results Fluorescent videomicroscopy through a special ''floating'' objective that allows a series of lenses to move in unison with the beating dog heart was used on the left ventricular surface of open-chest dogs. Epicardial microvessels (25 to 130 mu m), in focus throughout the cardiac cycle, were recorded after infusion of acridine orange (to fluorescently label leukocytes) during either 1 hour of ischemia followed by 2 hours of reperfusion, 3 hours of ischemia, or 3 hours of no ischemia. The amount of net fluorescence recorded along microvessel walls, which represented leukocyte accumulation, significantly increased in dogs during reperfusion (n=8) compared with the same time period in the animals that were kept ischemic (n=5) (21.0+/-3.8 versus 10.9+/-4.5 gray scale; P=.0001). The rapid increase in fluorescence during reperfusion was also significantly different from values in the same group during the preceding period of ischemia (21.0+/-3.8 versus 5.1+/-2.1 gray scale; P=.0001), whereas no significant increase was seen over the same time periods in the animals that remained ischemic throughout the protocol.Conclusions Reperfusion, compared with ischemia alone, promotes the rapid accumulation of leukocytes in the coronary microvasculature of jogs.