The no reflow phenomenon: a time-limiting factor for reperfusion after coronary occlusion?

A study was performed in 33 dogs to ascertain (1) whether the "no reflow" phenomenon is a critical factor determining the time beyond which revascularization can no longer salvage ischemic myocardium, and (2) whether reperfusion damages tissue not otherwise destined to become necrotic. Twelve dogs were subjected to 2 hours of coronary occlusion followed by 4 hours of reperfusion, 10 dogs to 4 hours of occlusion followed by 2 hours of reperfusion and 11 dogs to 6 hours of coronary occlusion alone. The area of "no reflow" was determined by injecting a fluorescent dye into the left atrium at the end of 6 hours with the coronary artery patent, and the ischemic area at risk by injecting methylene blue dye into the left atrium with the coronary artery reoccluded. The area of necrosis on all 5 mm transverse ventricular sections was determined by incubation in triphenyltetrazolium chloride stain and compared with its respective area at risk and area of no reflow. In all dogs the no reflow area was always significantly smaller than, and contained topographically within, the area of necrosis. Furthermore, the area of necrosis expressed as a percent of the area at risk was significantly smaller for dogs with 2 or 4 hours of occlusion and reperfusion than for dogs with longer periods of occlusion and briefer periods of reperfusion. It is concluded that (1) the no reflow phenomenon does not determine the critical time for salvageability of myocardium by revascularization because the area of no reflow is surrounded by necrotic but reperfusable tissue, and (2) reperfusion does not increase the quantity of ischemic tissue that becomes necrotic.