This investigation aims to determine whether the temporal relationship between myocardial perfusion and rate of glucose uptake can be used to differentiate acute myocardial ischemia from infarction. This hypothesis has been derived from positron emission tomographic studies (PET) in patients and in dogs, but has not yet been validated by high resolution isotopic studies or by histological investigations. We will use quantitative autoradiography (QARG) which has a resolution 150 times greater than PET. Absolute uptake of T1-201 by the myocardium will measure coronary arterial flow. Absolute uptake of C14- DG by the myocardium will measure rate of glucose uptake. QARG maps of perfusion and glucose uptake will be correlated with cell viability (or necrosis) of adjacent myocardial sections using histochemical techniques for early evidence of necrosis (TTC stain) and histological techniques for delayed evidence of necrosis (light microscopy). The left anterior descending coronary artery in dogs will be occluded for 15 min, 40 min and 180 min (Groups A-F). Groups A, C, and E will be reperfused for 3 hrs. and animals will then be sacrificed. Groups B, D, and F will be reperfused for 48 hrs. and animals will then be sacrificed. Thus, a wide pathological spectrum will exist from: a) ischemia with high-energy phosphate depletion but no necrosis; b) subendocardial necrosis; and c) transmural necrosis. This spectrum will permit detailed study of the temporal relationships between myocardial flow-glucose uptake, flow-histology (or histochemistry), and glucose uptake-histology (or histochemistry), which exist during acute myocardial ischemia and infarction. The results should have wide implications to the: 1) early diagnostic differentiation between myocaridal ischemia and infarction; 2) assessment of medical and surgical therapies designed to limit infarct size; and 3) validation of the current PET data derived in patients and animals.
