Pyruvate is an intermediate of glycolysis that is rapidly extracted and metabolized by normal myocardium but accumulates as lactate in ischemic myocardium. Based on these facts, the principal investigator in a prior study administered 14C-pyruvate to normal and ischemic isolated perfused hearts and intraatrially into open-chested rabbits and found that more 14C accumulated in ischemic than in normal regions of myocardium. The purpose of the present proposal is to define the time course for myocardial extraction of labeled pyruvate after experimental coronary occlusion and determine whether the concentration of radioactivity is different in reversibly and irreversibly injured regions of myocardium. Accordingly, open-chested dogs will undergo experimental coronary occlusion and subsequently be given 14C-pyruvate intraatrially at 15 minutes, 3 hours, 6 hours or 24 hours after occlusion. Myocardial biopsies will be taken two minutes and 15 minutes after 14C-pyruvate injection and analyzed for concentration of radioactivity, lactate, pyruvate and glycogen. In addition, to assess for myocardial necrosis, tissue LDH and CK enzyme levels will be determined and compared to a sample of the same tissue incubated in triphenyl tetrazolium chloride (TTC), which stains normal and reversibly injured myocardium 14C-radioactivity will be compared to tissue enzyme activity and TTC staining to determine whether an increased ratio of radioactivity (ischemic/normal) is present only in reversibly injured myocardium or whether it is also present in irreversibly injured myocardium. Subsequent studies in close-chested dogs will be carried out using 11C-pyruvate, a positron emitting radionuclide in conjunction with a positron computed tomographic carera currently undergoing construction at The University of Texas Health Science Center at Houston. Regional extraction and metabolism of 11C-pyruvate will be determined and compared with regional wall motion and post mortem TTC staining. The potential significance of this study is to determine whether 11C-pyruvate will be useful in delineating ischemic yet still viable myocardium as a region of increased radioactivity using positron computed tomography in man.
NIH ExPorter
NIH ExPorter