title: Mechanisms of carvedilol action in human congestive heart failure.
abstract: The precise mechanism by which beta-adrenoceptor blockers exert their beneficial actions in patients with heart failure remains unclear. Several possibilities have been proposed, including heart rate reduction, beta2-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.
authors.affiliation: Department of Cardiovascular Medicine, Alfred Hospital and Baker Medical Research Institute, Melbourne, Australia. david.kaye@baker.edu.au
authors.forename: D M
authors.initials: DM
authors.lastname: Kaye
authors.forename: L
authors.initials: L
authors.lastname: Johnston
authors.forename: G
authors.initials: G
authors.lastname: Vaddadi
authors.forename: H
authors.initials: H
authors.lastname: Brunner-LaRocca
authors.forename: G L
authors.initials: GL
authors.lastname: Jennings
authors.forename: M D
authors.initials: MD
authors.lastname: Esler
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D011941:Receptors, Adrenergic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002227:Carbazoles; D011412:Propanolamines; D011941:Receptors, Adrenergic; D000077261:Carvedilol