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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

Lookup NU author(s): Professor Bob Anderson

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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 mu g.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 mu g.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.

Publication metadata

Author(s): Schmitt B, Li TY, Kutty S, Khasheei A, Schmitt KRL, Anderson RH, Lunkenheimer PP, Berger F, Kuhne T, Peters B

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology - Heart and Circulatory Physiology

Year: 2015

Volume: 309

Issue: 1

Pages: H45-H52

Print publication date: 01/07/2015

Online publication date: 17/04/2015

ISSN (print): 0363-6135

ISSN (electronic): 1522-1539

Publisher: American Physiological Society

URL: http://dx.doi.org/10.1152/ajpheart.00746.2014

DOI: 10.1152/ajpheart.00746.2014

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