NEUROHUMORAL AND HEMODYNAMIC-EFFECTS IN C OMBINATION THERAPY WITH ENOXIMONE AND DOPAMINE

Twelve patients with severe heart failure (NYHA class III - IV) were i nvestigated by intraindividual comparison for the hemodynamic and neur ohumoral effects of dopamine (3 and 6 mu g/kg/min), enoximone (8 mu g/ kg/min), and the combination of both medications (dopamine 3 mu g/kg/ min + enoximone 8 mu g/kg/min) using right heart catheterization. The duration of active treatment was 8 h for each substance with a subsequ ent washout time of 16 h. Dopamine led to a dose-dependent increase in cardiac index of 10 - 13% and 18 - 37% under 3 and 6 mu g/kg/min, res pectively (p < 0.001). Enoximone monotherapy produced a comparable inc rease in cardiac index between 27 and 32% (p < 0.001). Enoximone, but not dopamine, resulted in a significant decrease in mean pulmonary art ery pressure (21 - 26%; p < 0.01), pulmonary capillary wedge pressure (24 - 30%; p < 0.01), and right atrial mean pressure (26 - 28%; p < 0. 001). The systemic vascular resistance was without significant changes at low-dose dopamine therapy, decreased by 10 - 19% insignificantly a t a dose of 6 mu g/kg/min, and reached the level of significance with enoximone therapy (- 20 to - 25%; p < 0.001). There was a highly signi ficant decrease by 49 - 55% in systemic vascular resistance with enoxi mone (p < 0.001), in contrast to dopamine. Heart rate and blood pressu re remained without significant changes at low-dose dopamine, with the heart rate increasing significantly by 25% at a dose of 6 mu g/kg/min within the first 2 h (p < 0.01). Enoximone produced a heart rate incr ease by 8 - 13% (being significant after 2 h; p < 0.05) with no change s in blood pressure. The combination therapy with dopamine and enoximo ne led to an additive increase in cardiac index by 35 - 43% (p < 0.001 ), a decrease in right atrial mean pressure by 28 - 36% (p < 0.01), a decrease in systemic vascular resistance by 27 - 30% (p < 0.01) and in pulmonary vascular resistance by 46 - 51%. An additive effect on hear t rate was not observed. The respective monotherapies with low-dose do pamine and enoximone had no remarkable effect on plasma catecholamines , while dopamine at a dose of 6 mu g/kg/min and combination therapy le d to a significant increase in noradrenaline levels. There was a highl y significant decrease in the plasma concentration of the atrial natri uretic factor under enoximone and combination therapy (p < 0.001) as w ell as a significant decrease in aldosterone (0 < 0.05). Our findings confirm the additive hemodynamic effects on cardiac output, right and left ventricular filling pressures and vascular resistances, thus reco mmending combination therapy with low-dose dopamine and enoximone for acute treatment of severe heart failure as a favorable therapeutic app roach.