Diltiazem administered before or during myocardial ischemia decreases adenine nucleotide catabolism.
Calcium antagonists potentially prevent ATP breakdown, but literature data on this subject are conflicting. We studied the effect of diltiazem on ATP catabolism in rat heart, perfused according to Langendorff. Administration of the drug took place either before or during ischemia, induced by lowering the perfusion pressure. The reduction in flow without diltiazem was 85%. We observed a significantly (P less than 0.001) lower production of purine nucleosides and oxypurines by the ischemic heart, when we gave diltiazem in a dose range of 1 to 100 microM before ischemia. The highest drug concentration reduced purine release by 85%. Due to ischemia, myocardial adenine nucleotide content decreased by 40% (P less than 0.001); this was partially prevented by 5 microM diltiazem (P = 0.4 v. untreated hearts). The drug also effectively reduced purine release, when applied five minutes after the induction of ischemia, but higher concentrations were needed.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014527:Uric Acid / Q000378:metabolism; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
D000227:Adenine Nucleotides; D001552:Benzazepines; D007042:Hypoxanthines; D014970:Xanthines; D010725:Phosphocreatine; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D007288:Inosine; D000255:Adenosine Triphosphate; D004110:Diltiazem; D000241:Adenosine