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

Autor(es)

Teixeira-Fonseca, Jorge Lucas ; de Lima Conceicao, Michael Ramon ; Leal-Silva, Polyana ; Roman-Campos, Danilo

• Tipo de documento: Artigo Científico
• Fonte: BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY; v. 132, n. 5, p. 10-pg., 2023-03-01.

Resumo

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. (AU)

• Processo FAPESP: 19/21304-4 - Mecanismos arritmogênicos em doenças do coração direito
• Beneficiário: Danilo Roman Campos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/05584-7 - Avaliação da toxicidade aguda e crônica ao coração e ao cérebro expostos a pesticidas encontrados na água potável do Brasil
• Beneficiário: Danilo Roman Campos
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2