Comparison of the effects of bepridil and diltiazem upon globally ischemic rat hearts.
Effects of the Ca2+ antagonists, bepridil (20 microM) and diltiazem (2.5 microM), upon ischemia/reperfusion injury were assessed in perfused, working rat hearts. These treatments were equally cardiodepressant in non-ischemic hearts. A lower concentration (5 microM) of bepridil was also assessed. Hearts which were reperfused following 33 min of global ischemia recovered 12.8% of preischemic pressure-rate product and had markedly reduced ATP, total adenine nucleotides, ATP/ADP ratio, and mitochondrial function. Treatment with bepridil before and during ischemia did not improve recovery of cardiac function, tissue energy reserves, or mitochondrial function upon reperfusion with control buffer. Control hearts treated with bepridil had normal levels of high energy compounds. Treatment with diltiazem significantly improved contractile function, and metabolic parameters. Ischemia/reperfusion injury was associated with a doubling of tissue Ca2+ content. Pretreatment with diltiazem, but not bepridil, reduced Ca2+ overload. Bepridil did not directly protect the myocardium from ischemia/reperfusion injury perhaps due to its inability to prevent Ca2+ overload.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015764:Bepridil; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011759:Pyrrolidines; D000244:Adenosine Diphosphate; D015764:Bepridil; D000255:Adenosine Triphosphate; D004110:Diltiazem; D002118:Calcium