Effects of diltiazem upon globally ischemic rat hearts.
Addition of diltiazem (0.0, 0.95, 2.5 or 7.5 microM) to isolated working rat hearts before and during ischemia, produced a concentration-dependent increase in recovery of contractile function. Recovery of post-ischemic pressure-rate product showed a strong relationship with depression of pre-ischemic pressure-rate product, primarily from decreased heart rate before ischemia and increased pressure development following reperfusion. Increased recovery in treated hearts was associated with higher ATP and adenine nucleotide levels (ADN), but no relationship was observed between energy levels and degree of recovery of function or concentration of diltiazem. Hearts made ischemic for 20 min without reperfusion had increased ATP and decreased lactic acid accumulation when treated with 7.5 microM diltiazem. The results indicate contractile-dependent mechanisms of action of diltiazem in global ischemic hearts which can only be partly explained by preservation of ATP and ADN, but also are associated with reduced lactic acid accumulation.
D000227:Adenine Nucleotides / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006019:Glycolysis; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D007773:Lactates; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D004110:Diltiazem