No reflow after acute myocardial infarction is an important predictor of infarct size and clinical outcome. However, the exact relationship between no reflow and infarct size remains to be determined, particularly because no reflow may progress during the time course of reperfusion. Control groups of five previous protocols using the anesthetized, open-chest rabbit model of coronary artery occlusion and reperfusion were retrospectively analyzed with respect to the correlation between regional myocardial blood flow (RMBF; radioactive microspheres) and infarct size (triphenyltetrazolium chloride) in the course of reperfusion. After 30 min of occlusion, reflow (defined as the ratio of RMBF in the risk area divided by the nonischemic area) declined from hyperemic values after 30 min of reperfusion (reflow ratio: 1.33 +/- 0.81; RMBF in the risk area at the same time point: 2.25 +/- 1.04 ml x g(-1) x min(-1)) to 0.47 +/- 0.22 after 120 min and 0.46 +/- 0.13 after 180 min of reperfusion. After 120 min of ischemia, reflow at 30 min of reperfusion was 0.49 +/- 0.24 and deteriorated by 120 min of reperfusion (0.26 +/- 0.15). In every group, there was a strong correlation between infarct size and reflow (correlation coefficients: -0.62 to -0.82). The lines of regression for the groups with assessment of RMBF after 120 or 180 min of reperfusion were nearly identical regardless of the duration of ischemia. Thus microvascular reperfusion injury led to a striking decrease in RMBF within the first 2 h of reperfusion, with infarct size as the major determinant of reflow at a given time point of reperfusion.