RESUMEN
Atrial arrhythmias (AA) are common in pulmonary hypertension (PH) and are closely associated with poor clinical outcomes. One of the most studied models to investigate PH is the rat model of monocrotaline (MCT) induced PH (MCT-PH). To date, little is known about right atrium (RA) function in the MCT-PH model and the propensity of RA to develop arrhythmias. Therefore, the aim of the study was to evaluate the function of the RA of control (CTRL) and MCT treated rats, and the ability of amiodarone, a classical antiarrhythmic, to prevent the occurrence of AA in the RA in MCT-PH rats. RA function was studied in MCT-PH rats 20 days after a single subcutaneous injection of MCT 50 mg/kg. The histological results indicated the presence of RA and right ventricular hypertrophy. Surface electrocardiogram demonstrated increased P wave duration, PR wave duration and QT interval in MCT rats. RA from MCT rats were more susceptible to develop ex vivo burst pacing arrhythmias when compared to CTRL. Intriguingly, amiodarone in clinical relevant concentration was not able to prevent the occurrence arrhythmias in RA from MCT-PH animals. Hence, we conclude that the rat model of MCT-PH impairs RA structure and function, and acute exposure of RA to amiodarone in clinical relevant concentration is not able to attenuate the onset of arrhythmias in the ex vivo RA preparation.
RESUMEN
The TASK-1 channel belongs to the two-pore domain potassium channel family. It is expressed in several cells of the heart, including the right atrial (RA) cardiomyocytes and the sinus node, and TASK-1 channel has been implicated in the pathogenesis of atrial arrhythmias (AA). Thus, using the rat model of monocrotaline-induced pulmonary hypertension (MCT-PH), we explored the involvement of TASK-1 in AA. Four-week-old male Wistar rats were injected with 50 mg/kg of MCT to induce MCT-PH and isolated RA function was studied 14 days later. Additionally, isolated RA from six-week-old male Wistar rats were used to explore the ability of ML365, a selective blocker of TASK-1, to modulate RA function. The hearts developed right atrial and ventricular hypertrophy, inflammatory infiltrate and the surface ECG demonstrated increased P wave duration and QT interval, which are markers of MCT-PH. The isolated RA from the MCT animals showed enhanced chronotropism, faster contraction and relaxation kinetics, and a higher sensibility to extracellular acidification. However, the addition of ML365 to extracellular media was not able to restore the phenotype. Using a burst pacing protocol, the RA from MCT animals were more susceptible to develop AA, and simultaneous administration of carbachol and ML365 enhanced AA, suggesting the involvement of TASK-1 in AA induced by MCT. TASK-1 does not play a key role in the chronotropism and inotropism of healthy and diseased RA; however, it may play a role in AA in the MCT-PH model.
Asunto(s)
Fibrilación Atrial , Hipertensión Pulmonar , Animales , Masculino , Ratas , Atrios Cardíacos/patología , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/patología , Hipertrofia Ventricular Derecha/inducido químicamente , Hipertrofia Ventricular Derecha/patología , Modelos Teóricos , Monocrotalina/efectos adversos , Ratas WistarRESUMEN
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 with experimental model. Using a burst pacing protocol, the isolated right atrium from the monocrotaline-treated animals was 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 remodelling, which increased the susceptibility to present ex vivo atrial arrhythmias, and the antiarrhythmic drug ranolazine ameliorated the phenotype.