NSAIDs, which are widely prescribed, have raised serious concerns about cardiovascular safety in previous studies. To investigate the duration of the action potential at 90% of repolarization, QT intervals, and effective refractory period (ERP), 38 hearts of the New Zealand White rabbit were harvested and retrogradely perfused using a Langendorff setup.
After gathering baseline data, the following drugs were perfused through the hearts:
- indomethacin (group 2, n=13; 10μM and 20μM),
- diclofenac (group 3, n=13; 10μM and 20μM),
- ibuprofen (group 1, n=12; 10μM and 30μM).
Pacing protocols were repeated for each concentration of each drug. Perfusion of NSAIDs resulted in significant and reproducible shortening of APD90 and QT intervals in all groups. Under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations, the arrhythmia susceptibility was markedly changed as monomorphic ventricular tachycardia was observed more frequently in all groups.
An established rabbit whole-heart model shows that ibuprofen, indomethacin, and diclofenac perfusions produced arrhythmia susceptibility, but the action potential duration (APD) shortening and shortened ERP were critical to arrhythmogenesis.