P-31-NUCLEAR MAGNETIC-RESONANCE STUDIES OF CHRONIC MYOCARDIAL-ISCHEMIA IN THE YUCATAN MICROPIG

In this work, an x-irradiation/high fat/high cholesterol diet-induced atherogenic model was invoked to examine the effects of severe diffuse atherosclerosis on myocardial metabolism in the in vivo porcine heart . This model was studied using spatially localized P-31-nuclear magnet ic resonance (NMR) to monitor pH and the levels of inorganic phosphate , phosphomonoesters, creatine phosphate, and adenosine triphosphate as a function of workload transmurally in control swine and in animals s uffering from chronic ischemic heart disease. These preliminary studie s revealed that the development of severe atherosclerosis and the acco mpanying chronically diseased state produce changes in high energy pho sphates and that increases in rate pressure products result in demonst rable signs of ischemia in the myocardium which span the entire left v entricular wall. Ischemic changes include a global increase in inorgan ic phosphate and corresponding decreases in creatine phosphate, ATP, a nd pH. Importantly, changes in intracellular pH are noted with even th e slightest increase in workload suggesting that these diseased hearts display elevated glycolytic activity. By challenging these animals wi th increased cardiac workload, we directly visualize how the chronical ly compromised heart responds to severe oxygen challenges in a clinica lly relevant model of this situation.