Lack of sustained hemodynamic effects of the beta 2-adrenoceptor agonist dopexamine in end-stage congestive heart failure

Abstract

In congestive heart failure (CHF), a permanent βadrenergic stimulus is imposed on the heart by a compensatory activation of the sympathetic nervous system, which results in increased serum levels of norepinephrine. 1 Since norepinephrine acts primarily on cardiac β 1 adrenoceptors, there is a selective down-regulation of β 1 adrenoceptors with a preserved β 2-adrenoceptor subpopulation in the myocardium from patients with end-stage CHF. 2,3 These laboratory findings strongly suggest that stimulation of β 2 adrenoceptors could provide additional inotropic support to the myocardium in terminal CHF and, hence, might be therapeutically useful in such patients. Dopexamine is a β 2-sympathomimetic compound structurally related to dopamine with no activity on β 1, α 1 and α 2 adrenoceptors. 4 In a number of clinical trials, dopexamine has been shown to produce beneficial effects in patients with New York Heart Association heart failure, class II to IV. 5 Herein, we report the effects of dopexamine on hemodynamics in 4 patients with terminal CHF due to dilated cardiomyopathy before cardiac transplantation. Four patients (aged 41, 51, 47 and 61 years) with dilated cardiomyopathy were monitored by right-sided heart catheterization in the intensive care unit. All patients had most severe CHF, and were receiving concomitant therapy with dopamine (1.5 to 2 μg/min/kg body weight) and dobutamine (10 to 14 μg/min/kg body weight) was necessary to maintain blood pressure. None of the patients had to be ventilated. Systolic blood pressure was 90 to 100 mm Hg at entry to the study. The protocol of the study is shown in Figure 1. After a 12-hour equilibration period, doses of dopexamine were increased stepwise from 1 to 6 μg/min/kg body weight. Hemodynamic measurements were taken immediately before and after a 2-hour infusion period of dopexamine at each dose of the drug. After this, patients were maintained on 6 μg/ min/kg body weight dosage, and measurements were again taken at 4 to 8 hours during continuation of this dose. The accompanying medication of dopamine and dobutamine was not altered. All patients received digoxin and furosemide. Digoxin serum levels were in the therapeutic range. Two patients were in sinus rhythm and 2 patients had atrial fibrillation. The study protocol was approved by the ethical committee of the University of Munich and was conducted in accordance with the Declaration of Helsinki.