Teixeira-Fonseca Jorge Lucas, Joviano-Santos Julliane Vasconcelos, da Silva Alcântara Fabiana, de Lima Conceição Michael Ramon, Leal-Silva Polyana, Roman-Campos Danilo
Laboratory of Cardiobiology, Department of Biophysics, Paulista School of Medicine, Federal University of Sao Paulo, São Paulo, Brazil.
Post-Graduate Program in Health Sciences, Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte, Brazil.
Clin Exp Pharmacol Physiol. 2023 Nov;50(11):893-902. doi: 10.1111/1440-1681.13813. Epub 2023 Aug 23.
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.
房性心律失常（AA）在肺动脉高压（PH）中很常见，并且与不良临床结局密切相关。用于研究PH的最常用模型之一是野百合碱（MCT）诱导的PH大鼠模型（MCT-PH）。迄今为止，对于MCT-PH模型中的右心房（RA）功能以及RA发生心律失常的倾向知之甚少。因此，本研究的目的是评估对照（CTRL）大鼠和接受MCT治疗的大鼠的RA功能，以及经典抗心律失常药物胺碘酮预防MCT-PH大鼠RA中AA发生的能力。在单次皮下注射50 mg/kg MCT后20天，对MCT-PH大鼠的RA功能进行研究。组织学结果显示存在RA和右心室肥大。体表心电图显示MCT大鼠的P波时限、PR波时限和QT间期增加。与CTRL相比，MCT大鼠的RA在体外爆发性起搏时更易发生心律失常。有趣的是，临床相关浓度的胺碘酮无法预防MCT-PH动物RA中心律失常的发生。因此，我们得出结论，MCT-PH大鼠模型损害了RA的结构和功能，并且在临床相关浓度下将RA急性暴露于胺碘酮并不能减轻体外RA制剂中心律失常的发生。
