Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline- induced pulmonary hypertension.

Atrial arrhythmias are a hallmark of heart diseases. The antiarrhythmic drug ranolazine with multichannel blocker properties is a promising agent to treat atrial arrhythmias. We therefore used the rat model of monocrotaline-induced pulmonary-hypertension to assess whether ranolazine can reduce the incidence of ex vivo atrial arrhythmias in isolated right atrium. Four-week-old Wistar rats were injected with 50 mg/kg of monocrotaline, and isolated right atrium function was studied 14 days later. The heart developed right atrium and right ventricular hypertrophy, and the ECG showed an increased P wave duration and QT interval, which are markers of the disease. Moreover, monocrotaline injection caused enhanced chronotropism, and faster kinetics of contraction and relaxation in isolated right atrium. Additionally, in a concentration-dependent manner, ranolazine showed chronotropic and ionotropic effects upon isolated right atrium, with higher potency in the control when compared to experimental model. Using a burst pacing protocol, the isolated right atrium from the monocrotaline treated animals were more susceptible to develop arrhythmias and ranolazine was able to attenuate the phenotype. Thus, we concluded that the rat model of monocrotaline-induced pulmonary-hypertension develops right atrium remodeling which increased the susceptibility to present ex vivo atrial arrhythmias and the antiarrhythmic drug ranolazine ameliorated the phenotype.