Sustained hemodynamic improvement during long-term therapy with levodopa in heart failure: role of plasma catecholamines.
Long-term therapy with oral sympathomimetic amines in patients with heart failure has been limited by the eventual development of diminished pharmacologic efficacy. However, a previous investigation in five subjects with heart failure suggested that long-term ingestion of levodopa, which is decarboxylated endogenously to dopamine, produces a sustained improvement in cardiac function. In the present study, levodopa was administered orally (1.5 to 2.0 g) to 14 patients with heart failure while hemodynamic responses and plasma catecholamines were monitored. Initially, an increase in cardiac index and stroke volume index was accompanied by a decline in systemic vascular resistance, mean pulmonary capillary wedge pressure and mean right atrial pressure. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of dopamine rose substantially after drug ingestion and correlated significantly with changes in cardiac index (r = 0.73, p less than 0.05). After 12 weeks of treatment with levodopa, the changes in cardiac index, stroke volume index, systemic vascular resistance and plasma dopamine levels persisted (n = 12 patients). Moreover, a significant decrease occurred in the heart rate at rest. Although there was an initial tendency for plasma norepinephrine concentrations to increase, a return to control levels was documented after long-term treatment. Thus, tolerance to the hemodynamic actions of levodopa did not develop during long-term administration of the drug. The hemodynamic responses observed can be ascribed to the activation of beta 1-adrenoceptors and dopamine1 receptors by dopamine generated from levodopa. The dopamine2 activity of dopamine does not appear to be responsible for the improvement in cardiac performance produced by levodopa.
Rajfer
S I
SI
Section of Cardiology, University of Chicago, Illinois 60637.
Rossen
J D
JD
Nemanich
J W
JW
Douglas
F L
FL
Davis
F
F
Osinski
J
J
D000328:Adult; D000368:Aged; D002302:Cardiac Output; D002395:Catecholamines / Q000097:blood*; D004298:Dopamine / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011669:Pulmonary Wedge Pressure; D013997:Time Factors; D014655:Vascular Resistance
D002395:Catecholamines; D007980:Levodopa; D004298:Dopamine; D009638:Norepinephrine