LEUKOCYTE ADHESION TO THE CORONARY MICROVASCULATURE DURING ISCHEMIA AND REPERFUSION IN AN IN-VIVO CANINE MODEL

Background Prompt reperfusion of ischemic myocardium or myocardium tha t is in the process of becoming infarcted is a cornerstone of current therapy for coronary artery disease. Paradoxically, experimental evide nce suggests that cardiac damage may be caused by the reperfusion itse lf. Leukocyte attachment to the coronary vascular endothelium during r eperfusion may be an initiating step in this detrimental process. Leuk ocyte adhesion to microvascular endothelium has never been demonstrate d directly in a cardiac model of ischemia and reperfusion. Methods and Results Fluorescent videomicroscopy through a special ''floating'' ob jective that allows a series of lenses to move in unison with the beat ing dog heart was used on the left ventricular surface of open-chest d ogs. Epicardial microvessels (25 to 130 mu m), in focus throughout the cardiac cycle, were recorded after infusion of acridine orange (to fl uorescently label leukocytes) during either 1 hour of ischemia followe d by 2 hours of reperfusion, 3 hours of ischemia, or 3 hours of no isc hemia. 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 t he 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 reper fusion 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 g ray scale; P=.0001), whereas no significant increase was seen over the same time periods in the animals that remained ischemic throughout th e protocol. Conclusions Reperfusion, compared with ischemia alone, pro motes the rapid accumulation of leukocytes in the coronary microvascul ature of jogs.