ABSTRACT
290Reperfusion of ischemic myocardium may be followed by incomplete restoration of blood flow, a phenomenon known as “no-reflow”. Although “no-reflow” has been viewed as something already established at the moment of reperfusion, this study was designed to determine whether “delayed” no-reflow may be seen as a manifestation of progressive reperfusion injury to the microvasculature and/or myocardium. In 15 open-chest dogs, the circumflex coronary artery was transiently occluded for 90 min. Animals were reperfused for 2 min (n = 7) or 3.5 h (n = 8), and regional myocardial blood flow was measured with microspheres at end-ischemia and 2 min of reperfusion and also at 30 min and 3.5 h of reperfusion in the long-reperfusion group. After the last flow measurement, injections were made into the left atrium of thioflavin S (to identify areas of no-reflow) and monastral blue (to delineate the risk region) and the hearts were removed, sectioned, and observed under UV light. We found the extent of no-reflow to be three times larger in dogs reperfused for 3.5 h than those reperfused for 2 min (25.9 vs. 9.5% of the risk region, p <0.05), indicating that “delayed” no-reflow was actually more important than “immediate” noreflow. Blood flow during ischemia in both the “immediate” and “delayed” no-reflow tissue was virtually zero. In most myocardial samples demonstrating “delayed” no-reflow, early reperfusion was substantial, usually >1 ml/min/g, but there was a marked and progressive decline in flow over time. In contrast, samples from within the risk zone (usually also within the infarct) demonstrating thioflavin uptake had higher levels of initial reperfusion, and although flow decreased over time, it usually did not fall below baseline levels. Electron microscopic studies showed that both “immediate” and “delayed” no-reflow were associated with severe injury to the vascular endothelium and myocytes, although “immediate” no-reflow was associated with coagulative necrosis and “delayed” no-reflow with contraction band necrosis. The results are consistent with the hypothesis that “delayed” noreflow represents a progressive, reperfusion-related injury to both the microvasculature and myocardium.
