The influence of inhibitors of the ATP degradative pathway on recovery of function and high energy phosphate after transient ischemia in the rat heart.
The loss of the catabolic products of adenosine triphosphate in the form of purine nucleosides and oxypurines during ischemia and subsequent reperfusion may limit adenine nucleotide regeneration. This study compared the effects of infusion of inhibitors of the major reactions involved in the degradation of adenosine triphosphate to inosine on the postischemic recovery of high energy phosphate and myocardial function. Inhibitors of adenylate kinase, 5'nucleotidase, adenosine translocase and adenosine deaminase were studied. Following 30 minutes of ischemia, only hearts infused with alpha, beta, methylene adenosine diphosphate (5' nucleotidase inhibitor) recovered significantly better ventricular function than control (p less than 0.05), but all hearts had increased adenosine triphosphate regeneration (p less than 0.05). The formation and washout of greater than 30% of the total adenine pool metabolites was not prevented by any drug. Nevertheless all manipulations of adenine metabolism resulted in recruitment of high energy phosphate during preischemic infusion.
D015720:5'-Nucleotidase; D000208:Acute Disease; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000263:Adenylate Kinase / Q000037:antagonists & inhibitors; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism*; D015226:Dinucleoside Phosphates; D008297:Male; D009708:Nucleotidases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000227:Adenine Nucleotides; D058892:Adenosine Deaminase Inhibitors; D015226:Dinucleoside Phosphates; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D013868:Thioinosine; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C010192:9-(2-hydroxy-3-nonyl)adenine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase; D009708:Nucleotidases; D015720:5'-Nucleotidase; C001789:4-nitrobenzylthioinosine; D000225:Adenine; D000241:Adenosine