ISCHEMIA PRODUCES AN INCREASE IN AMMONIA OUTPUT IN SWINE MYOCARDIUM

We have recently reported that ischemia causes myocardial ammonia prod uction which is not due to amino acid breakdown. The purpose of this s tudy was to identify the remaining possible sources of ammonia product ion. The prospects were either deamination of AMP to inosine monophosp hate (IMP), or adenosine to inosine. Eight intact extracorporally perf used pig hearts were rendered regionally ischemic by reducing the left anterior descending coronary artery blood flow by 60% for 40 minutes. Adjacent myocardium supplied by the circumflex artery was held aerobi c throughout the study. Myocardial oxygen consumption and regional sys tolic shortening in the left anterior descending perfusion bed fell by 50 and 32%, respectively. Myocardial ammonia production increased sig nificantly (p=0.008) and tissue ammonia concentration was 55% greater in the ischemic left anterior descending bed than in the aerobic circu mflex bed (p=0.003). Compared to the circumflex bed, ATP and creatine phosphate concentrations in the left anterior descending bed were decr eased by 41 and 53%, respectively. There was no significant increases in AMP or IMP levels, however there were dramatic increases of 525 and 397% in adenosine and inosine levels in the ischemic tissue. Thus, my ocardial ammonia production was stimulated by ischemia without an incr ease in IMP levels. Combined with the fact that adenylate deaminase le vels in the swine myocardium are normally low, this leads to the likel y conclusion that source of the increased myocardial ammonia productio n during ischemia is deamination of adenosine, not IMP formation from AMP.