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.