The effects of Cholestasis on the Heart

Abstract

Objective: High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation, and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Methods and Results: Multicellular human atrial preparations (‘trabeculae’) were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with atrial fibrillation and ECG parameters analyzed. Additionally, we conducted electrophysiological studies in murine myocytes and assessed expression of bile acid transporters and receptors in human hearts. Taurocholic acid concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300µM TCA, p

Date of Award	2015
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Burkert Mathias Pieske (Supervisor), Michael Trauner (Supervisor) & Dirk von Lewinski (Supervisor)