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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2020-09-01
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doaj-78d9b779398c45159eddde8c4749c2722021-09-19T11:26:10ZengNature Publishing GroupScientific Reports2045-23222020-09-0110111310.1038/s41598-020-72016-4Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat heartsElisa Ferraro0Lidia Pozhidaeva1David S. Pitcher2Catherine Mansfield3Jia Han Benjamin Koh4Catherine Williamson5Oleg Aslanidi6Julia Gorelik7Fu Siong Ng8National Heart and Lung Institute, Imperial College LondonSchool of Biomedical Engineering and Imaging Science, King’s College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonSchool of Biomedical Engineering and Imaging Science, King’s College LondonDepartment of Women and Children’s Health, King’s College LondonSchool of Biomedical Engineering and Imaging Science, King’s College LondonNational Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonAbstract 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.https://doi.org/10.1038/s41598-020-72016-4 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisa Ferraro Lidia Pozhidaeva David S. Pitcher Catherine Mansfield Jia Han Benjamin Koh Catherine Williamson Oleg Aslanidi Julia Gorelik Fu Siong Ng |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-09-01 |
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. |
url |
https://doi.org/10.1038/s41598-020-72016-4 |
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