National Heart and Lung Institute, Imperial College London, London, UK.
School of Biomedical Engineering and Imaging Science, King's College London, London, UK.
Sci Rep. 2020 Sep 17;10(1):15284. doi: 10.1038/s41598-020-72016-4.
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.
急性心肌缺血再灌注（I-R）是冠心病患者室性心律失常的主要原因。熊去氧胆酸（UDCA）先前已被证明在胎儿心脏中具有抗心律失常作用。本研究旨在探讨 UDCA 是否能预防成年心肌缺血再灌注引起的心律失常，并比较急性（仅灌注）与长期（预处理 2 周加灌注）UDCA 给药的效果。Langendorff 灌注的成年 Sprague-Dawley 大鼠心脏通过结扎左前降支（10 分钟）引起急性区域性缺血，随后进行再灌注（2 分钟），并定量心律失常的发生率。长期 UDCA 给药可降低急性缺血性心律失常的发生率（p=0.028），与急性治疗相比，缺血期室性早搏的数量减少（10±3 次 vs 58±15 次，p=0.036）。急性 UDCA 给药组未观察到抗心律失常作用。急性和长期 UDCA 治疗均未改变再灌注心律失常的发生率。UDCA 的抗心律失常作用可能部分通过增加心脏波长来介导，这归因于传导速度减慢的减弱（p=0.03），以及急性缺血期间 Connexin43 磷酸化的保留（p=0.0027）。长期 UDCA 给药的潜在抗心律失常作用值得进一步研究。
