title: Effects of incremental beta-blocker dosing on myocardial mechanics of the human left ventricle: MRI 3D-tagging insight into pharmacodynamics supports theory of inner antagonism.
abstract: Beta-blockers contribute to treatment of heart failure. Their mechanism of action, however, is incompletely understood. Gradients in beta-blocker sensitivity of helically aligned cardiomyocytes compared with counteracting transversely intruding cardiomyocytes seem crucial. We hypothesize that selective blockade of transversely intruding cardiomyocytes by low-dose beta-blockade unloads ventricular performance. Cardiac magnetic resonance imaging (MRI) 3D tagging delivers parameters of myocardial performance. We studied 13 healthy volunteers by MRI 3D tagging during escalated intravenous administration of esmolol. The circumferential, longitudinal, and radial myocardial shortening was determined for each dose. The curves were analyzed for peak value, time-to-peak, upslope, and area-under-the-curve. At low doses, from 5 to 25 μg·kg(-1)·min(-1), peak contraction increased while time-to-peak decreased yielding a steeper upslope. Combining the values revealed a left shift of the curves at low doses compared with baseline without esmolol. At doses of 50 to 150 μg·kg(-1)·min(-1), a right shift with flattening occurred. In healthy volunteers we found more pronounced myocardial shortening at low compared with clinical dosage of beta-blockers. In patients with ventricular hypertrophy and higher prevalence of transversely intruding cardiomyocytes selective low-dose beta-blockade could be even more effective. MRI 3D tagging could help to determine optimal individual beta-blocker dosing avoiding undesirable side effects.
authors.affiliation: Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany; schmitt@dhzb.de.
authors.forename: Boris
authors.initials: B
authors.lastname: Schmitt
authors.affiliation: Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany;
authors.forename: Tieyan
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pediatric Cardiology, University of Nebraska Medical Center, Children's Hospital and Medical Center, Omaha, Nebraska;
authors.forename: Shelby
authors.initials: S
authors.lastname: Kutty
authors.affiliation: Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany;
authors.forename: Alireza
authors.initials: A
authors.lastname: Khasheei
authors.affiliation: Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany;
authors.forename: Katharina R L
authors.initials: KR
authors.lastname: Schmitt
authors.affiliation: Institute of Medical Genetics, Newcastle University, Newcastle upon Tyne, United Kingdom; and.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Anderson
authors.affiliation: Department of Experimental Thoracic and Cardiovascular Surgery, University Hospital Münster, Münster, Germany.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Lunkenheimer
authors.affiliation: Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany;
authors.forename: Felix
authors.initials: F
authors.lastname: Berger
authors.affiliation: Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany;
authors.forename: Titus
authors.initials: T
authors.lastname: Kühne
authors.affiliation: Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany;
authors.forename: Björn
authors.initials: B
authors.lastname: Peters
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D005260:Female; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C036604:esmolol
keywords: MRI; beta-blockers; left ventricular hypertrophy