Bile acids induce arrhythmias in human atrial myocardium—implications for altered serum bile acid composition in patients with atrial fibrillation

摘要: Objective High bile acid serum concentrations have been implicated in cardiac disease, particularly arrhythmias. Most data originate from vitro studies and animal models. We tested the hypotheses that (1) high are arrhythmogenic adult human myocardium, (2) composition altered patients with atrial fibrillation (AF) (3) therapeutically used ursodeoxycholic has different effects than other potentially toxic acids. Methods Results Multicellular preparations (‘trabeculae’) were exposed to primary acids incidence of arrhythmic events was assessed. Bile measured samples 250 their association AF ECG parameters analysed. Additionally, we conducted electrophysiological murine myocytes. Taurocholic (TCA) concentration-dependently induced arrhythmias trabeculae (14/28 at 300 µM TCA, p + /Ca 2+ exchanger (NCX) tail current density afterdepolarisations. Inhibition NCX prevented trabeculae. Conclusions TCA induce atria while does not. is associated higher levels non-ursodeoxycholic conjugates low conjugates. These suggest (arrhythmogenic) protective create a milieu decreased threshold thus may facilitate events.