Dexamethasone and ursodeoxycholic acid protect against the arrhythmogenic effect of taurocholate in an in vitro study of rat cardiomyocytes
Dexamethasone and ursodeoxycholic acid protect against the arrhythmogenic effect of taurocholate in an in vitro study of rat cardiomyocytes
复制标题
DOI：
10.1016/s1470-032(03)02973
复制
发表时间：
2003-05-01
影响因子：
5.8
通讯作者：
Williamson, C
中科院分区：
文献类型：
--
作者：
Gorelik, J;Shevchuk, AI;Williamson, C
目的探讨熊去氧胆酸和地塞米松对牛磺胆酸所致心律失常的体外保护作用。设计实验室研究。伦敦帝国理工学院哈默史密斯校区。新生大鼠心肌细胞样本。方法采用扫描离子电导显微镜观察1 ~ 2日龄大鼠心室肌细胞的收缩速率、收缩节律、收缩幅度及钙离子动态变化。细胞在地塞米松（80或800 nM）或0.1 mM熊去氧胆酸中预孵育16小时，然后加入不同浓度的牛磺胆酸（0.3-4.5 mM）。主要观察指标为收缩速率和幅度的变化、钙动力学和节律。结果牛磺胆酸盐浓度达3mm时可引起异常变化，包括收缩速率、收缩幅度、钙动力学异常和心律失常。虽然地塞米松对这些变化没有直接的保护作用，但预先用地塞米松孵育是有保护作用的。结论地塞米松和熊去氧胆酸对牛磺胆酸对心肌细胞的致心律失常作用具有保护作用。
Objective To establish whether the therapeutic agents ursodeoxycholic acid and dexamethasone protect cardiomyocytes from taurocholate-induced arrhythmias in an in vitro model.Design Laboratory study.Setting Imperial College London, Hammersmith Campus.Sample Neonatal rat cardiomyocytes.Methods Using scanning ion conductance microscopy, we measured the rate, rhythm, amplitude of contraction and calcium dynamics of ventricular myocytes from one to two day old rats. Cells were pre-incubated for 16 hours in dexamethasone (80 or 800 nM) or 0.1 mM ursodeoxycholic acid before adding taurocholate at different concentrations (0.3-4.5 mM).Main outcome measures Changes in rate and amplitude of contraction, calcium dynamics and rhythm.Results Taurocholate at concentrations of up to 3 mM induces abnormal changes including reductions in rate, amplitude of contraction, abnormal calcium dynamics and dysrhythmias. Although dexamethasone had no immediate protective effect on these changes, pre-incubation with dexamethasone was protective. Ursodeoxycholic acid pre-incubation was protective at taurocholate concentrations up to 1 MM.Conclusion The therapeutic agents dexamethasone and ursodeoxycholic acid appear protective against the arrhythmogenic effect of taurocholate on cardiomyocytes.