title: Protection by bepridil against myocardial ATP-catabolism is probably due to negative inotropy.
abstract: The protective effect of calcium antagonists on ischemic heart has been attributed to decreased energy expenditure. We administered one of the newer calcium antagonists, DL-bepridil (0.1-10 microM), to Langendorff rat hearts 10 or 15 min before ischemia (flow reduction approximately 80%). Vasodilation during normoxia was already observed with 0.3 microM DL-bepridil (flow increase 34%, p less than 0.005). This concentration decreased normoxic contractility and ischemic purine release, a marker for ATP breakdown. In the absence of bepridil, purine release of hearts that were made ischemic was 8.5-fold higher than that of normoxic control hearts. With 1 microM bepridil, the ischemic purine efflux was suppressed by 55% (p less than 0.05), with negative inotropy (p greater than 0.05) during normoxia. At 3 and 10 microM, bepridil decreased normoxic contractility by 40 and 75%, respectively (p less than 0.001), concomitant with a decrease in ischemic purine release by 80 and 76%, respectively (p less than 0.01). At the end of ischemia, myocardial ATP and creatine phosphate had decreased by 22 and 55%, respectively (p less than 0.05), and ADP, AMP, and creatine had increased 1.5-3.5-fold (p less than 0.05). Bepridil (3 microM) normalized the adenine nucleotide values; creatine and creatine phosphate approached control levels. The dose-dependent protection of the ischemic heart by bepridil appears to arise from its negative inotropic action during normoxia.
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015764:Bepridil; D003864:Depression, Chemical; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism
chemical_list: D007042:Hypoxanthines; D011759:Pyrrolidines; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine; D007288:Inosine; D015764:Bepridil; D000255:Adenosine Triphosphate; D000241:Adenosine