P6591Arrhythmogenic effects of non-steroidal anti-inflammatory drugs (NSAID)

Abstract

Listen

Translate article

Abstract Background Clinical and experimental data suggest potential deleterious effects of non-steroidal anti-inflammatory drugs (NSAID) in cardiac disease. The aim of the present study was to characterize potential direct arrhythmogenic effects of ibuprofen or indometacin on cardiac electrophysiology. Methods and results In 13 isolated rabbit hearts, indometacin was administered in increasing concentrations (10, 30 and 50μM) after obtaining baseline data. In further 13 hearts, ibuprofen was infused (10, 30 and 50μM). Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant decrease of QT-interval in indometacin- (50μM: −60ms, p<0.05) and ibuprofen-treated hearts (50μM: −81ms, p<0.01). This was accompanied by a similar decrease of action potential duration (APD). Effective refractory period (ERP) was also reduced by indometacin (−24ms, p<0.05) and ibuprofen (−22ms, p<0.05) while spatial dispersion of repolarisation remained stable with both drugs. Programmed ventricular stimulation and burst stimulation were employed for provocation of ventricular arrhythmias. In the indomethacin group 7 episodes of ventricular arrhythmias were inducible at baseline. The incidence was increased to 22 (10μM), 37 (30μM) and 51 (50μM) with higher concentrations of indometacin. In the ibuprofen group 15 episodes were inducible at baseline. After infusion of 10μM ibuprofen, also 15 episodes of ventricular arrhythmias occurred while 34 episodes were inducible with 30μM ibuprofen. Conclusion Infusion of the NSAID ibuprofen and indometacin resulted in a significant abbreviation of myocardial repolarization and a shortening of ventricular refractory periods. This resulted in an enhanced inducibility of ventricular arrhythmias and may contribute to the proposed deleterious effects of NSAID in the presence of cardiac disease.