Electromechanical dissociation and possible uncoupling of phosphorylation following tachydysrhythmogenic dose of amrinone in the guinea-pig Langendorff heart preparation.
In the guinea-pig Langendorff heart preparation amrinone induced tachydysrhythmia and electromechanical dissociation at 1000 micrograms/ml but not at 50 and 250 micrograms/ml. At 1000 micrograms/ml, the myocardial oxygen consumption was twice the value at equilibration in spite of a very marked fall in contractile force, thus suggesting that amrinone at that toxic dose level uncoupled phosphorylation. Amrinone at 50 and 250 micrograms/ml caused a dose-related reversal of the cardiac depressant effect induced by verapamil suggesting, therefore, that the positive inotropic effect is due at least in part to influx of Ca2+ into the sarcoplasm. It is suggested that the electromechanical dissociation and the possible uncoupling of phosphorylation induced by a toxic dose of amrinone are related to a considerable influx of Ca2+ into the sarcoplasm and the mitochondria.
D000631:Aminopyridines / Q000494:pharmacology*; D000676:Amrinone; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004562:Electrocardiography; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000631:Aminopyridines; D002316:Cardiotonic Agents; D014475:Uncoupling Agents; D014700:Verapamil; D000676:Amrinone