Short-term synchronized retroperfusion before reperfusion reduces infarct size after prolonged ischemia in dogs

Abstract

Background. Previous studies have demonstrated that synchronized coronary venous retroperfusion (SRP) can restore blood flow to the ischemic myocardium, resulting in infarct size reduction and improvement of the left ventricular function. Despite the nutritive blood flow achieved by SRP being relatively limited, SRP has been shown to improve washout of by-products from the ischemic myocardium. The aim of this study was to investigate whether short-term SRP immediately prior to reperfusion would attenuate the deteriorative phenomena following reperfusion. Methods and Results. Closed-chest anesthetized dogs underwent 3 hours of left anterior descending coronary artery (LAD) occlusion. The dogs were then randomized into two groups: (1) control group (n=9), in which the occlusion was immediately followed by 3-hour reperfusion; or (2) SRP group (n=9), in which SRP was started 3 hours after occlusion and maintained for 30 minutes with sustained occlusion followed by 2.5-hour reperfusion with simultaneous discontinuation of SRP. There were no statistical differences between the groups in global hemodynamics and degree of ischemia measured by radiolabeled microspheres. Myocardial infarct size (triphenyltetrazolium method) expressed as percentage of risk area was significantly smaller in the SRP group (24 ± 7%, mean ± SEM) than in the control group (54 ± 9%). The extent of myocardial hemorrhage expressed as percentage of infarct size was also significantly reduced in the SRP group (3 ± 2%) compared with the control group (24 ± 6%). The increase in end-diastolic wall thickness in the ischemic area after reperfusion assessed by two-dimensional echocardiography was significantly less in the SRP group. Blood flow measurements after reperfusion demonstrated the occurrence of no-reflow phenomenon only in the control group. Histological examination revealed extensive myocardial hemorrhages only in the control group, which extended into the nonnecrotic myocardium in four of nine hearts and extensive contraction band necrosis compared with the SRP group. Conclusions. Short-term SRP prior to reperfusion can reduce infarct size, myocardial hemorrhage, wall swelling, and no-reflow phenomenon. The mechanism of this beneficial effect is not clear but might be due to gradual reperfusion and washout of by-products from the ischemic myocardium before fully oxygenated arterial blood reperfusion.