Effects of prostaglandin E1, dobutamine and placebo on hemodynamic, renal and neurohumoral variables in patients with advanced heart failure.
Excessive neurohumoral activity remains a major burden to the circulation of patients with advanced heart failure. Prostaglandin E1 (PGE1), a balanced i.v. vasodilator, was shown to elicit favorable hemodynamic and clinical effects in this cohort. A prospective randomized parallel group trial was performed to evaluate acute, intermediate and chronic changes in hemodynamic, neurohumoral and renal variables in response to PGE1, dobutamine and placebo. Thirty patients with class III and IV heart failure and low cardiac index (mean 1.9 l/min/m2) two hours after oral drugs including high dose enalapril were included. A 7-day-infusion of PGE1 (16.5 +/- 5 ng/kg/min, range 10 to 20 ng/kg/min, group A n = 10), dobutamine (4.5 +/- 1 micrograms/kg/min, range 2.5 to 5 micrograms/kg/min, group B n = 10) or placebo (saline, group C n = 10) was administered via a central venous access line after stepwise titration until intolerable side effects developed with PGE1 or a 20% increase in cardiac index occurred with dobutamine, which was continued on this dose throughout while PGE1 was maintained on 50% peak dose. Hemodynamic data were collected at baseline, at peak dosages, after 12 hours and after 7 days. Of neurohumoral variables plasma norepinephrine, big endothelin (Big ET) and atrial natriuretic peptide (ANP) were simultaneously evaluated using RIA methods. Renal plasma flow (by paraaminohippurate clearance) and glomerular filtration rate (by iothalamate clearance) was measured prior to and during the infusions (after 12 hours and after 7 days). At peak dose and at 12 hours significant drops from baseline of mean pulmonary artery pressure, pulmonary capillary wedge pressure and systemic vascular resistance were observed which were accompanied by a rise in cardiac output with both PGE1 and dobutamine. These changes were maintained through 7 days when pulmonary vascular resistance levels also fell with both active drugs. Blood pressure did not change throughout, but PGE1 increased heart rate slightly at 12 hrs. Both PGE1 and dobutamine enhanced renal plasma flow after 7 days, but only PGE1 decreased glomerular filtration fraction significantly. Glomerular filtration rate did not change with either drug. PGE1 decreased ANP levels at 12 hrs, and dobutamine increased big ET levels at peak, but decreased big ET at 7 days. Norepinephrine levels were unaffected throughout. Except a slight decrease in right atrial pressure after 7 days placebo did not change any measured variable significantly. Taken together, these data suggest that treatment with PGE1 is as efficacious as low-dose dobutamine in improving cardiac performance and renal perfusion in advanced heart failure. Of importance, no deleterious neurohumoral counterregulation was observed with PGE1.
Wimmer
A
A
Department of Cardiology, University of Vienna, Austria.
Stanek
B
B
Kubecova
L
L
Vitovec
J
J
Spinar
J
J
Yilmaz
N
N
Kos
T
T
Hartter
E
E
Frey
B
B
Pacher
R
R
D000527:Alprostadil / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use*; D016232:Endothelins / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011446:Prospective Studies; D012079:Renal Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D016232:Endothelins; D014665:Vasodilator Agents; D004280:Dobutamine; D009320:Atrial Natriuretic Factor; D000527:Alprostadil; D009638:Norepinephrine