Effects of bosentan, sildenafil and their combination on T-wave amplitude and QT ınterval in a rat model of pulmonary hypertension

Abstract

Aim: Although, bosentan and sildenafil have been used to treat PAH, the effect of these drugs on electrocardiographic (ECG) changes are still unclear. The aim of this study is to evaluate the effects of bosentan, sildenafil, and their combination on T-wave amplitude and QT interval in rats with monocrotaline (MCT)-induced PAH. Materials and Methods: Saline (control) or MCT were applied to sixty-six male Wistar rats. By the development of PAH (4th week), MCT-given rats were randomized into 4 groups and were treated orally with bosentan, sildenafil and combination of sildenafil and bosentan or placebo for 3 weeks. Echocardiographic (ECHO) and ECG examinations were performed three times on baseline, 4th and 7th week. Results: ECHO results showed that the application of MCT developed PAH in all injected rats. Usually, T-wave changes and QTc prolongation in ECG began after PAH and T-wave amplitudes, T-repolarization time as well as QTc intervals significantly increased in all groups after treatment (p<0.001). Conclusion: Our experimental study suggest that T-wave changes and QTc prolongation to be more clear in combined treatment than the single use of sildenafil or bosentan in MCT-induced PAH. The most interesting finding in this research was that it could be predicted serious arrythmia with ECG changes (probably QTc interval) - clearly a future direction.