Mechanisms of Carvedilol Action in Human Congestive Heart Failure

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 37; no. 5; pp. 1216 - 1221
• Main Authors: Kaye, David M, Johnston, Leonie, Vaddadi, Gautam, Brunner-LaRocca, Hanspeter, Jennings, Garry L, Esler, Murray D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.05.2001; Hagerstown, MD Lippincott
• Subjects: Antihypertensive agents; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Blood Pressure - drug effects; Carbazoles - pharmacology; Carbazoles - therapeutic use; Cardiovascular system; Carvedilol; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart Rate - drug effects; Heart Ventricles - drug effects; Humans; Male; Medical sciences; Middle Aged; Oxygen Consumption - drug effects; Pharmacology. Drug treatments; Propanolamines - pharmacology; Propanolamines - therapeutic use; Receptors, Adrenergic - metabolism; Sympathetic Nervous System - drug effects; Cardiac performance; Vasodilator agent; Carbon dioxide; α1-Adrenergic receptor; Cardiovascular disease; β2-Adrenergic receptor; β-Adrenergic receptor; Vascular disease; Heart disease; Antagonist; Mechanism of action; Cerebrovascular disease; Human; Heart failure; Nervous system diseases; Oxygen consumption; Left ventricle; Cerebral disorder; Heart rate; Chemotherapy; Treatment; Carvedilol; Central nervous system disease; Antihypertensive agent; Norepinephrine; Hemodynamics; Beta blocking agent; Ejection fraction
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.37.5.1216

ABSTRACT—The precise mechanism by which β-adrenoceptor blockers exert their beneficial actions in patients with heart failure remains unclear. Several possibilities have been proposed, including heart rate reduction, β2-adrenoceptor–mediated modulation of catecholamine release, antagonism of the receptor-mediated toxic actions of norepinephrine on the myocardium, and favorable effects on myocardial energetics. In the present study we evaluated the effect of 3 months of carvedilol therapy on hemodynamics, total systemic and cardiac norepinephrine spillover (isotope dilution method), and myocardial metabolism (myocardial oxygen consumption and carbon dioxide release) in 10 patients with severe congestive heart failure. Although carvedilol treatment was associated with a significant improvement in left ventricular ejection fraction (17±1% to 28±3%;P <0.01) and left ventricular stroke work (87±13 to 119±21 g · m per beat;P <0.05), this effect was unrelated to changes in total systemic or cardiac norepinephrine spillover. The rise in left ventricular stroke work was accompanied by a modest rise in myocardial oxygen consumption per beat (0.33±0.04 to 0.42±0.04;P =0.05), although contractile efficiency was unchanged. The favorable effects of carvedilol on ventricular function in the failing heart are not explained by alterations in norepinephrine release or by changes in myocardial contractile efficiency.