Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol.
OBJECTIVE
We compared the hemodynamic effects of dobutamine and enoximone administration before and after long-term beta-blocker therapy with metoprolol or carvedilol in patients with chronic heart failure (HF).


BACKGROUND
Patients with HF on beta-blocker therapy may need hemodynamic support with inotropic agents, and the hemodynamic response may be influenced by both the inotropic agent and the beta-blocker used.


METHODS
The hemodynamic effects of dobutamine (5 to 20 microg/kg/min intravenously) and enoximone (0.5 to 2 mg/kg intravenously) were assessed by pulmonary artery catheterization in 29 patients with chronic HF before and after 9 to 12 months of treatment with metoprolol or carvedilol at standard target maintenance oral doses. Hemodynamic studies were performed after >/=12 h of wash-out from all cardiovascular medications, except the beta-blockers that were administered 3 h before the second study.


RESULTS
Compared with before beta-blocker therapy, metoprolol treatment decreased the magnitude of mean pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP) decline during dobutamine infusion and increased the cardiac index (CI) and stroke volume index (SVI) response to enoximone administration, without any effect on other hemodynamic parameters. Carvedilol treatment abolished the increase in heart rate, SVI, and CI and caused a rise, rather than a decline, in PAP, PWP, systemic vascular resistance, and pulmonary vascular resistance during dobutamine infusion. The hemodynamic response to enoximone, however, was maintained or enhanced in the presence of carvedilol.


CONCLUSIONS
In contrast with its effects on enoximone, carvedilol and, to a lesser extent, metoprolol treatment may significantly inhibit the favorable hemodynamic response to dobutamine. No such beta-blocker-related attenuation of hemodynamic effects occurs with enoximone.
Metra
Marco
M
Cattedra di Cardiologia, Università di Brescia, Brescia, Italy. metramarco@libero.it
Nodari
Savina
S
D'Aloia
Antonio
A
Muneretto
Claudio
C
Robertson
Alastair D
AD
Bristow
Michael R
MR
Dei Cas
Livio
L
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D017335:Enoximone / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D011875:Radionuclide Angiography; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D002316:Cardiotonic Agents; D011412:Propanolamines; D000077261:Carvedilol; D004280:Dobutamine; D017335:Enoximone; D008790:Metoprolol