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

Abstract Acute myocardial ischaemia and 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 pro...

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Autores principales:	Elisa Ferraro, Lidia Pozhidaeva, David S. Pitcher, Catherine Mansfield, Jia Han Benjamin Koh, Catherine Williamson, Oleg Aslanidi, Julia Gorelik, Fu Siong Ng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78d9b779398c45159eddde8c4749c272
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spelling	oai:doaj.org-article:78d9b779398c45159eddde8c4749c2722021-12-02T18:33:51ZProlonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts10.1038/s41598-020-72016-42045-2322https://doaj.org/article/78d9b779398c45159eddde8c4749c2722020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-72016-4https://doaj.org/toc/2045-2322Abstract Acute myocardial ischaemia and 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, and compares the 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 min), followed by reperfusion (2 min), and arrhythmia incidence quantified. Prolonged UDCA administration reduced the incidence of acute ischaemia-induced arrhythmias (p = 0.028), with a reduction 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 may be partially mediated by an increase in cardiac wavelength, due to the 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.Elisa FerraroLidia PozhidaevaDavid S. PitcherCatherine MansfieldJia Han Benjamin KohCatherine WilliamsonOleg AslanidiJulia GorelikFu Siong NgNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisa Ferraro Lidia Pozhidaeva David S. Pitcher Catherine Mansfield Jia Han Benjamin Koh Catherine Williamson Oleg Aslanidi Julia Gorelik Fu Siong Ng Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
description	Abstract Acute myocardial ischaemia and 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, and compares the 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 min), followed by reperfusion (2 min), and arrhythmia incidence quantified. Prolonged UDCA administration reduced the incidence of acute ischaemia-induced arrhythmias (p = 0.028), with a reduction 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 may be partially mediated by an increase in cardiac wavelength, due to the 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.
format	article
author	Elisa Ferraro Lidia Pozhidaeva David S. Pitcher Catherine Mansfield Jia Han Benjamin Koh Catherine Williamson Oleg Aslanidi Julia Gorelik Fu Siong Ng
author_facet	Elisa Ferraro Lidia Pozhidaeva David S. Pitcher Catherine Mansfield Jia Han Benjamin Koh Catherine Williamson Oleg Aslanidi Julia Gorelik Fu Siong Ng
author_sort	Elisa Ferraro
title	Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
title_short	Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
title_full	Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
title_fullStr	Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
title_full_unstemmed	Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
title_sort	prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/78d9b779398c45159eddde8c4749c272
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Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts

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