Beneficial hemodynamic effects of oral levodopa in heart failure. Relation to the generation of dopamine.
Among the positive inotropic drugs available to improve myocardial contractility in congestive heart failure, only digitalis glycosides are suitable for oral administration. In this study, we administered oral levodopa (1.5 to 2.0 g), which is decarboxylated to form dopamine, to 10 patients with severe congestive heart failure. Peak hemodynamic responses occurred one hour after the ingestion of levodopa, with the mean (+/- S.E.M.) cardiac index increasing from 1.8 +/- 0.1 to 2.4 +/- 0.2 liters per minute per square meter of body-surface area (P less than 0.01) and systemic vascular resistance declining from 1905 +/- 112 to 1513 +/- 121 dyn X sec X cm-5 (P less than 0.01). These effects persisted for four to six hours. Left ventricular filling pressure, heart rate, and mean arterial pressure were unchanged. Plasma concentrations of dopamine rose to a peak level of 34 +/- 5 ng per milliliter one hour after drug ingestion and decreased toward base line over the ensuing five hours. A significant correlation was observed between plasma dopamine levels and changes in cardiac index (r = 0.8; P less than 0.02). Five patients enrolled in a trial to evaluate the effectiveness of long-term therapy with levodopa had similar hemodynamic responses to the drug after 6.8 +/- 1.7 months of treatment. Thus, oral administration of levodopa to patients with severe heart failure produced a sustained improvement in cardiac function. The hemodynamic responses observed can be attributed to the activation of beta 1-adrenergic, dopamine, and dopamine receptors by dopamine derived from levodopa.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D003653:Decarboxylation; D004298:Dopamine / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D013997:Time Factors
D007980:Levodopa; D004298:Dopamine