title: In patients chronically treated with metoprolol, the demand of inotropic catecholamine support after coronary artery bypass grafting is determined by the Arg389Gly-beta 1-adrenoceptor polymorphism.
abstract: In vitro, the Arg389Gly-beta(1)-adrenoceptor (AR) polymorphism exhibits decreased receptor signaling. In vivo, dobutamine infusion evoked smaller heart rate and/or contractility increases in subjects carrying Gly389Gly-beta(1)AR vs subjects carrying Arg389Arg-beta(1)AR. The aim of this study was to find out whether the Arg389Gly-beta(1)AR polymorphism might also determine demand of catecholamine-induced inotropic support in patients with low cardiac index (CI) after coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB). For this purpose, we assessed in 82 patients, who were preoperatively chronically treated with metoprolol, after CABG surgery with CPB, the dose and duration of adrenaline-induced inotropic support in relation to the Arg389Gly-beta(1)AR genotype. Patients homozygous for the Arg389-beta(1)AR variant (n = 45) required, in comparison to patients homozygous for the Gly389-beta(1)AR variant (n = 9), lower adrenaline doses (53 +/- 24 vs 164 +/- 39 ng/kg body weight/min, p < 0.05) to reach a stable and comparable hemodynamic status and a CI >or= 3.0 l/min/m(2). Moreover, the time necessary for inotropic support tended to be shorter in patients homozygous for the Arg389-beta(1)AR than in patients homozygous for the Gly389-beta(1)AR (10.5 +/- 6 vs 20.5 +/- 12 h). Values for patients heterozygous for the Arg389Gly-beta(1)AR (n = 28) were in between. We conclude that the Arg389Gly-beta(1)AR polymorphism appears to be a determinant of cardiac responses to catecholamine stimulation. Thus, by assessment of the Arg389Gly-beta(1)AR polymorphism, it might be possible to predict demand of and therapeutic responses to beta AR agonist treatment.
authors.affiliation: Department of Pathophysiology and Nephrology, University of Essen School of Medicine, Hufelandstr. 55, 45147, Essen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Leineweber
authors.forename: Petra
authors.initials: P
authors.lastname: Bogedain
authors.forename: Christina
authors.initials: C
authors.lastname: Wolf
authors.forename: Sören
authors.initials: S
authors.lastname: Wagner
authors.forename: Melanie
authors.initials: M
authors.lastname: Weber
authors.forename: Heinz-Günther
authors.initials: HG
authors.lastname: Jakob
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.forename: Thomas
authors.initials: T
authors.lastname: Philipp
authors.forename: Otto-Erich
authors.initials: OE
authors.lastname: Brodde
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D001120:Arginine / Q000235:genetics; D001794:Blood Pressure; D002302:Cardiac Output; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000601:surgery; D004837:Epinephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005998:Glycine / Q000235:genetics; D006339:Heart Rate; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
chemical_list: D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D001120:Arginine; D008790:Metoprolol; D005998:Glycine; D009638:Norepinephrine; D004837:Epinephrine