Historical perspectives and update of amrinone.

The pathophysiological understanding and management of acute and chronic heart failure have changed dramatically in the past decade. Since the early 1980s, a major effort has been made to develop nonglycosidic, noncatecholamine agents that combine inotropic and vasodilating properties, in order to treat myocardial dysfunction unresponsive to current therapy. Within this context, increasing attention has been paid to the role of intracellular cyclic adenosine monophosphate (cAMP) in myocardial contractility. The pharmacologic use of catecholamines to stimulate beta-receptors activates adenylate cyclase, which in turn leads to an increase in intracellular levels of cAMP. In addition, phosphodiesterase 3 (PDE 3) inhibition may prevent the degradation of cAMP, thus maintaining high intracellular levels of the substance. Intravenous amrinone has been shown clinically to improve hemodynamic status remarkably in the patient experiencing a low cardiac output syndrome, by increasing CO while decreasing filling pressures and pulmonary arterial pressures, without increasing myocardial O2 demand. This report will review several studies of different types of patients and explain the effects of amrinone alone and in combination with the more traditionally used catecholamines. It must be stressed that amrinone, in spite of its dual action of inotropy and vasodilation, should not be considered a rival to catecholamines but rather an enhancer of them, which clinicians should consider using in the early stages of therapy in many different settings.