Persistent changes in myocardial glucose metabolism in vivo during reperfusion of a limited-duration coronary occlusion

Abstract

Background - Rapid reperfusion of an occluded coronary artery salvages regional mechanical function, but this benefit may not be realized for hours or days because of postischemic stunning. Recovery from stunning is incompletely understood but may involve adaptive changes in heart glucose metabolism. Methods and Results - To examine whether reversible coronary occlusion produces sustained changes in regional glucose metabolism in vivo, we performed a 20-minute left coronary artery occlusion followed by 24 hours of open-artery reperfusion in intact rats. Coronary occlusion produced stunning of the anterolateral left ventricle that resolved over 24 hours. When examined at 24 hours, reperfused regions were fully contractile and viable by vital staining and microscopy but demonstrated 25% reduction in blood flow and 50% increased uptake of circulating glucose, as estimated by in vivo [13N]NH3 and [18F]fluorodeoxyglucose (FDG) tracer uptake. Reperfused regions had largely inactive glycogen synthase, low rates of glycogen synthesis, and persistent 50% glycogen depletion but increased flux of plasma [1-13C]glucose into myocardial [3-13C]alanine, indicating preferential shunting of imported glucose away from storage and into glycolysis. Conclusions - Sustained increases in regional glycolytic consumption of circulating glucose occur during reperfusion of a limited- duration coronary occlusion. This suggests a role for glycolytic ATP in the recovery from postischemic stunning in vivo. Furthermore, [13N]NH3/FDG regional mismatch may constitute a clinically accessible late metabolic signature of regional myocardial ischemia.