Intracoronary infusion of dobutamine to patients with and without severe congestive heart failure. Dose-response relationships, correlation with circulating catecholamines, and effect of phosphodiesterase inhibition.

Abstract

We infused dobutamine into the left main coronary artery of 24 patients with severe congestive heart failure (CHF) and 8 normal subjects without hemodynamic dysfunction. The maximal +dP/dt response to intracoronary (IC) dobutamine in CHF patients was only 37% of that in normals. This decrease in maximal response was not associated with a rightshift in the EC50 for dobutamine's effect on +dP/dt, or a decrease in the affinity of myocardial beta adrenergic receptors for dobutamine determined in vitro. In nine of the CHF patients, IC dobutamine infusion was followed by IC infusion of the phosphodiesterase inhibitor milrinone, and subsequently, by a second IC infusion of dobutamine. After IC milrinone, the increase in +dP/dt caused by IC dobutamine (74±10%) was significantly greater than that caused by the first infusion of dobutamine (52±11%; P < 0.003) or milrinone (42±6%; P < 0.001). Resting plasma norephinephrine was markedly elevated in CHF patients (837±208 ng/liter), but not in normal subjects (142±32 ng/liter); and the increase in +dP/dt caused by IC dobutamine was inversely related to resting plasma norepinephrine levels (r = -0.653; P < 0.001). IC dobutamine caused a dose-related decrease in plasma norepinephrine (maximal effect, -160±31 ng/liter, P < 0.001). Thus, (a) the maximal inotropic response to dobutamine is markedly depressed in patients with severe CHF, and is significantly greater after pretreatment with the phosphodiesterase inhibitor milrinone; (b) the impairment in inotropic response to dobutamine is inversely related to circulating norepinephrine levels; and (c) myocardial stimulation by dobutamine results in withdrawal of sympathetic tone.

Vitamin C Augments the Inotropic Response to Dobutamine in Humans With Normal Left Ventricular Function

“…The administration of dobutamine by the intravenous or intracoronary route is a well-established method of assessing ␤-adrenergic responsiveness in humans. 11,20,22 In this study, the vitamin C-mediated augmentation of the dobutamine response was similar in magnitude to that observed with parasympathetic blockade in humans with normal ventricular function 11 as well as nitric oxide synthase blockade in patients with CHF. 20 In the experimental group, it is unlikely that the inotropic response to the second dobutamine infusion was potentiated by the previous dobutamine infusion, because no significant difference in the dP/dt response was observed between successive dobutamine infusions in the control group.…”

Low-dose dobutamine responsiveness in idiopathic dilated cardiomyopathy: relation to exercise capacity and clinical outcome

“…In chronic heart failure, the sympathetic nervous system activity is chronically increased, leading to a variety of maladaptive changes in the regulation of cardiovascular function [23] . Betaadrenergic receptor pathway desensitization, a fundamental abnormality in chronic heart failure resulting from chronic activation of the sympathetic nervous system [24] , is the main determinant of the attenuated cardiac response to dobutamine [25][26][27] . It depends on the degree of myocardial failure as well as on on the nature Abbreviations as in previous Table. 930 D. Scrutinio et al…”

Cardiovascular effects of the novel Ca2+‐sensitiser EMD 57033 in pigs at rest and during treadmill exercise

“…Untoward sidee ects of increased cytosolic Ca 2+ levels include increased oxygen consumption and increased risk of arrhythmias (Katz, 1986). Moreover, in patients with impaired left ventricular pump function b-adrenergic receptor responsiveness is often decreased (Bristow et al, 1982;1986), thereby attenuating the e cacy of particularly the sympathomimetic agents (Colucci et al, 1988;van der Giessen et al, 1989). Over the past 15 years a class of drugs has emerged that stimulates cardiac contractile force at least in part by increasing the Ca 2+ sensitivity and, to a lesser extent, maximum Ca 2+ -induced contractile force of myocardial contractile proteins.…”