Differential effects of dobutamine and a phosphodiesterase inhibitor on early diastolic filling in patients with congestive heart failure.
OBJECTIVE
This study was designed to compare the influence of beta-adrenergic stimulation (dobutamine) and a selective phosphodiesterase inhibitor (MS-857) on left ventricular diastolic performance and Doppler transmitral flow velocity patterns in patients with congestive heart failure and to elucidate the mechanisms for changes in early diastolic filling induced by each agent.


BACKGROUND
Both beta-adrenergic agonists and phosphodiesterase inhibitors act through the cyclic adenosine monophosphate pathway. However, it is controversial whether they have similar effects on diastolic performance. No previous studies have investigated the effects of these agents on Doppler-derived measurements of diastolic filling. We hypothesized that they would have different effects on early diastolic filling in patients with congestive heart failure.


METHODS
Twenty patients with chronic congestive heart failure resulting from idiopathic dilated cardiomyopathy were randomized to receive intravenous infusion of dobutamine (5 micrograms/kg body weight per min, n = 10) or oral administration of MS-857 (15 mg, n = 10). Transmitral flow velocity patterns were obtained with simultaneous recordings of pressure-volume loops using a conductance catheter with a micromanometer tip before and after drug administration.


RESULTS
Left ventricular filling pressure was reduced by both agents. Dobutamine decreased the time constant of isovolumetric relaxation and increased the difference between pulmonary artery wedge pressure at the peak of the v wave and left ventricular minimal pressure (10 +/- 3 to 12 +/- 4 mm Hg, p < 0.01) and peak early filling velocity (47 +/- 7 to 56 +/- 11 cm/s, p < 0.01). The diastolic pressure-volume relation showed a leftward shift in all patients. In contrast, MS-857 did not affect the time constant but maintained the pressure difference (9 +/- 3 to 8 +/- 3 mm Hg, p = NS) and peak early filling velocity (50 +/- 7 to 49 +/- 12 cm/s, p = NS). The diastolic pressure-volume relation after MS-857 showed a downward shift in most patients.


CONCLUSIONS
These results indicate that beta-adrenergic stimulation and phosphodiesterase inhibitors have different effects on early diastolic filling through different mechanisms in patients with congestive heart failure.
Nagata
K
K
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Iwase
M
M
Sobue
T
T
Yokota
M
M
D000284:Administration, Oral; D001783:Blood Flow Velocity / Q000187:drug effects; D006328:Cardiac Catheterization; D003326:Coronary Circulation / Q000187:drug effects; D003971:Diastole / Q000187:drug effects*; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology*; D018619:Echocardiography, Doppler, Pulsed; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines; D016277:Ventricular Function, Left / Q000187:drug effects*
D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; D044005:Tetrahydroisoquinolines; C059136:MS 857; D004280:Dobutamine