Ischemia produces an increase in ammonia output in swine myocardium.
We have recently reported that ischemia causes myocardial ammonia production which is not due to amino acid breakdown. The purpose of this study was to identify the remaining possible sources of ammonia production. The prospects were either deamination of AMP to inosine monophosphate (IMP), or adenosine to inosine. Eight intact extracorporally perfused 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 aerobic throughout the study. Myocardial oxygen consumption and regional systolic shortening in the left anterior descending perfusion bed fell by 50 and 32%, respectively. Myocardial ammonia production increased significantly (p = 0.008) and tissue ammonia concentration was 55% greater in the ischemic left anterior descending bed than in the aerobic circumflex bed (p = 0.003). Compared to the circumflex bed, ATP and creatine phosphate concentrations in the left anterior descending bed were decreased by 41 and 53%, respectively. There were 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, myocardial ammonia production was stimulated by ischemia without an increase in IMP levels. Combined with the fact that adenylate deaminase levels in the swine myocardium are normally low, this leads to the likely conclusion that source of the increased myocardial ammonia production during ischemia is deamination of adenosine, not IMP formation from AMP.
Hacker
T A
TA
Biodynamics Laboratory, University of Wisconsin, Madison, USA.
Renstrom
B
B
Paulson
D
D
Liedtke
A J
AJ
stanley
W C
WC
D000227:Adenine Nucleotides / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001783:Blood Flow Velocity; D006339:Heart Rate; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D013552:Swine; D016277:Ventricular Function, Left
D000227:Adenine Nucleotides; D000641:Ammonia