Degradation of adenine nucleotides in ischemic and reperfused rat heart.
Complete cessation of flow in isolated rat hearts for 90 min resulted in a gradual breakdown of ATP and concomitant accumulation of degradation products, such as adenosine, inosine (major break-down product), hypoxanthine, and, to a lesser extent, xanthine. After 45 min of ischemia, the content and relative composition of purines hardly changed, whereas the AMP content continued to rise. This finding points to constraints on AMP degradation and flux through the degradation pathway from adenosine to uric acid in the ischemic heart. In myocardial preparations, the cells of which were deliberately disrupted by freezing and thawing before anoxic incubation, AMP did not accumulate and was finally converted to hypoxanthine. These results indicate that compartmentalization of substrates and enzymes is responsible for the observed preferential accumulation of AMP and inosine in the ischemic heart. Inhibition of hypoxanthine degradation is explained by the absence of oxygen. Restoration of flow and oxygen supply abolished the inhibition of metabolic flux. Accumulated purines were released into the coronary effluent and, concomitantly, further metabolized. Comparison of tissue levels of hypoxanthine, xanthine, and uric acid before reperfusion and the amounts released during reperfusion indicates that in rat myocardium substantial amounts of potentially hazardous xanthine oxidase-derived reactive oxygen species are likely to be formed during the early reperfusion phase.
Van Bilsen
M
M
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
van der Vusse
G J
GJ
Coumans
W A
WA
de Groot
M J
MJ
Willemsen
P H
PH
Reneman
R S
RS
D000227:Adenine Nucleotides / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D006439:Hemodynamics; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014969:Xanthine Oxidase / Q000502:physiology
D000227:Adenine Nucleotides; D014969:Xanthine Oxidase; D010100:Oxygen