Leukocyte Adhesion to the Coronary Microvasculature During Ischemia and Reperfusion in an In Vivo Canine Model

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Abstract
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 μm), 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 dogs.