Effects of dopamine on left ventricular afterload and contractile state in heart failure: Relation to the activation of beta1-adrenoceptors and dopamine receptors

Abstract

Although long-term therapy with oral beta-adrenoceptor agonists in patients with heart failure is generally associated with the development of diminished pharmacologic efficacy, the ingestion of levodopa, which is decarboxylated endogenously to dopamine, is associated with a sustained improvement in cardiac function. The beneficial hemodynamic actions of dopanine in patients with heart failure have been attributed to a positive inotropic effect that is mediated through activation of beta1-adrenoceptors. However, a reduction in left ventricular afterload resulting from the activation of dopamine receptors may also lead to an improvement in the performance of the failing heart.To ascertain the relative importance of the positive inotropic and afterload-reducing effects of dopamine in patients with heart failure, dopamine (2, 4, 6 μg/kg per min), dobutamine (2, 6, 10 μg/kg per min) and nitroprusside (0.125 to 2.0 μg/kg per min) were administered to 13 patients with dilated cardiontyopathy while monitoring left ventricular wall thickness and dimensions by echocardiography and left ventricular and aortic pressures with a micromanometer-tipped catheter. Altering left ventricular afterload, quantified as end-systolic circumferential wall stress, with nitroprusside allowed generation of the left ventricular end-systolic circumferential wall stress-velocity of fiber shortening relation that represented the baseline contractile state of the myocardium.Left ventricular velocity of fiber shortening was elevated during the administration of dobutamine and dopamine when compared with measurements obtained with nitroprusside at the same left ventricular end-systolic circumferential wall stress. Furthermore, left ventricular end-systolic wall stress decreased with dopamine but not with dobutamine. Thus, the beta1-adrenoceptor activity of dopamine and dobutamine augmented the contractile state of the myocardium. The reduction in left ventricular afterload induced by dopamine but not dobutamine may reflect activation of peripheral vascular dopamine receptors by the former.