Salvage of ischaemic myocardium by reperfusion: importance of collateral blood flow and myocardial oxygen demand during occlusion.

Abstract

Early reperfusion after coronary artery occlusion is used to treat acute myocardial infarction, but the factors that determine whether salvage of ischaemic myocardium actually occurs remain poorly defined. Differences in collateral blood flow to the region at risk, and haemodynamic variables during occlusion, may contribute to uncertainty as to the time beyond which reperfusion no longer reduces infarct size. To clarify this issue, open chest anaesthetised dogs underwent 1, 2, 3, 4, or 6 hours of left anterior descending coronary artery occlusion followed by reperfusion or permanent occlusion (n = 8 per group). Microspheres were injected before occlusion and 15 minutes after occlusion for regional myocardial blood flow determination, and heart rate and arterial blood pressure were measured before occlusion and 10 minutes and 30 minutes after occlusion. At 96 hours after occlusion haemodynamic variables were again measured; the animals were then killed, and occluded bed size was determined by in vitro dye perfusion. The area of necrosis was quantified from histological sections and expressed as a percentage of occluded bed size (AN/OB). If duration of occlusion is considered alone, reperfusion beyond two hours did not salvage ischaemic myocardium in this model. If the results for occlusion equal to and greater than two hours are combined, the mean area of necrosis (27(2)%) was significantly greater than that produced by one hour of occlusion followed by reperfusion (10(4)%). For the animals undergoing occlusion for two or more hours or permanent occlusion, collateral blood flow significantly influenced the area of necrosis. When epicardial flow during occlusion was high (greater than 0.30 ml X min-1 X g-1 tissue) 13 out of 14 dogs undergoing occlusion for two or more hours or permanent occlusion developed small (AN/OB less than 27%) infarcts (mean AN/OB 17(2)%). In contrast, when epicardial collateral flow was low (less than 0.30 ml X min-1 X g-1) 14 out of 23 animals had large (AN/OB greater than 27%) infarcts (mean AN/OB 34(3)%). For the 23 dogs in which epicardial flow was low, heart rate during occlusion significantly influenced infarct size: the 14 dogs that developed large infarcts (AN/OB greater than 27%) had a higher mean heart rate (152(6) beats X min-1) than the nine that developed small infarcts (AN/OB less than 27%) (130(5) beats X min-1; p less than 0.025). Thus reperfusion at one hour after occlusion salvaged ischaemic myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)