Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

Abstract

BACKGROUND Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVO2 in postischemic myocardium is unknown. To address these issues, chronically instrumented dogs were studied serially over 1 month after transient left anterior descending coronary artery (LAD) occlusion, using positron emission tomography. METHODS AND RESULTS Dynamic imaging protocols were used in conjunction with tracer kinetic models to quantify blood flow and metabolic rates. Myocardial sectors were defined as normal, predominantly reversibly injured, and infarct-containing, based on occlusion blood flow images and postmortem histochemistry. Myocardial blood flow and metabolism were homogeneous at baseline. During LAD occlusion for 3 hours, myocardial blood flow in reversibly injured and infarct-containing sectors (determined with 13NH3) was decreased to 46% and 23%, respectively, of blood flow in normal tissue. MVO2, determined with [1-11C]acetate, was decreased less than myocardial blood flow, consistent with increased oxygen extraction in the ischemic tissue. After reperfusion, blood flow normalized rapidly in reversibly injured tissue but remained depressed in infarct-containing sectors. Regional myocardial function, assessed by two-dimensional echocardiography, was severely depressed during occlusion and did not improve significantly until 1 week after reperfusion. MVO2 remained depressed after reperfusion in both reversibly injured and infarct-containing sectors, did not improve from occlusion levels until 1 week after reperfusion, and remained significantly depressed 1 month after reperfusion even in reversibly injured sectors; [1-11C]palmitate kinetics were also abnormal in postischemic tissue. As reported previously, glucose metabolic rates were increased relative to baseline in normal but not in postischemic tissue 3 hours after reperfusion. Subsequently, glucose metabolism tended to be higher in postischemic relative to normal myocardium. CONCLUSIONS The results demonstrate decreased oxidative metabolism in postischemic tissue, with concomitant abnormalities in palmitate kinetics and glucose metabolism. Oxidative metabolism and regional function demonstrated a parallel recovery with time.