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Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts

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Title: Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
Authors: Ferraro, E
Pozhidaeva, L
Pitcher, DS
Mansfield, C
Koh, JHB
Williamson, C
Aslanidi, O
Gorelik, J
Ng, FS
Item Type: Journal Article
Abstract: Acute myocardial ischaemiaand reperfusion (I-R) are major causes of ventricular arrhythmias in patients with a history of coronary artery disease. Ursodeoxycholic acid (UDCA)has previously been shown to be antiarrhythmic in fetal hearts.This study was performed to investigate if UDCA protects against ischaemia-induced and reperfusion-induced arrhythmias in the adult myocardium,43andcomparesthe effect of acute (perfusion only) versus prolonged (2 weeks pre-treatment plus perfusion) UDCA administration. Langendorff-perfused adult Sprague-Dawley rat hearts were subjected to acute regional ischaemia by ligation of the left anterior descending artery(10 minutes), followed by reperfusion (2 minutes), and arrhythmia incidence quantified. Prolonged UDCA administration reduced the incidence of acute ischaemia-induced arrhythmias (p=0.028),with a eduction in number of ventricular ectopic beats during the ischaemic phase compared with acute treatment(10±3 vs 58±15, p=0.036).No antiarrhythmic effect was observed in the acute UDCA administration group. Neither acute nor prolonged UDCA treatment altered the incidence of reperfusion arrhythmias.The antiarrhythmic effect of UDCA maybe partially mediated by an increase in cardiac wavelength, due tothe attenuation of conduction velocity slowing (p=0.03), and the preservation of Connexin43 phosphorylation during acute ischaemia(p=0.0027). The potential antiarrhythmic effects of prolonged UDCA administration merit further investigation.
Issue Date: 17-Sep-2020
Date of Acceptance: 7-Aug-2020
URI: http://hdl.handle.net/10044/1/82241
DOI: 10.1038/s41598-020-72016-4
ISSN: 2045-2322
Publisher: Nature Publishing Group
Start Page: 1
End Page: 13
Journal / Book Title: Scientific Reports
Volume: 10
Copyright Statement: © The Author(s) 2020. Tis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: British Heart Foundation
British Heart Foundation
British Heart Foundation
Funder's Grant Number: RG/16/3/32175
FS/18/59/34180
Publication Status: Published
Online Publication Date: 2020-09-17
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons