[Neurohumoral and hemodynamic effects in combination therapy of enoximone and dopamine].
Twelve patients with severe heart failure (NYHA class III-IV) were investigated by intraindividual comparison for the hemodynamic and neurohumoral effects of dopamine (3 and 6 micrograms/kg/min), enoximone (8 micrograms/kg/min), and the combination of both medications (dopamine 3 micrograms/kg/min+enoximone 8 micrograms/kg/min) using right heart catheterization. The duration of active treatment was 8 h for each substance with a subsequent 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 micrograms/kg/min, respectively (p < 0.001). Enoximone monotherapy produced a comparable increase in cardiac index between 27 and 32% (p < 0.001). Enoximone, but not dopamine, resulted in a significant decrease in mean pulmonary artery 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 at a dose of 6 micrograms/kg/min, and reached the level of significance with enoximone therapy (-20 to -25%; p < 0.001). There was a highly significant decrease by 49-55% in systemic vascular resistance with enoximone (p < 0.001), in contrast to dopamine. Heart rate and blood pressure remained without significant changes at low-dose dopamine, with the heart rate increasing significantly by 25% at a dose of 6 micrograms/kg/min within the first 2 h (p < 0.01). Enoximone produced a heart rate increase by 8-13% (being significant after 2 h; p < 0.05) with no changes in blood pressure. The combination therapy with dopamine and enoximone 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 heart rate was not observed. The respective monotherapies with low-dose dopamine and enoximone had no remarkable effect on plasma catecholamines, while dopamine at a dose of 6 micrograms/kg/min and combination therapy led to a significant increase in noradrenaline levels. There was a highly significant decrease in the plasma concentration of the atrial natriuretic factor under enoximone and combination therapy (p < 0.001) as well as a significant decrease in aldosterone (0 < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Mitrovic
V
V
Max-Planck-Institut für Physiologische und Klinische Forschung, Kerckhoff-Klinik GmbH, Bad Nauheim.
Neuzner
J
J
Opper
H
H
Thormann
J
J
Schlepper
M
M
D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000503:physiopathology; D006328:Cardiac Catheterization; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood*; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology; D004298:Dopamine / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D017335:Enoximone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology
D002395:Catecholamines; D017335:Enoximone; D004298:Dopamine
Neurohumorale und hämodynamische Effekte in der Kombinationstherapie von Enoximon und Dopamin.