Dexamethasone and ursodeoxycholic acid protect against the arrhythmogenic effect of taurocholate in an in vitro study of rat cardiomyocytes

Abstract

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.