Teixeira-Fonseca Jorge Lucas, 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, Sao Paulo, Brazil.
Basic Clin Pharmacol Toxicol. 2023 May;132(5):359-368. doi: 10.1111/bcpt.13845. Epub 2023 Mar 1.
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.
房性心律失常是心脏病的一个标志。具有多通道阻滞剂特性的抗心律失常药物雷诺嗪是一种有前景的治疗房性心律失常的药物。因此，我们使用了野百合碱诱导的肺动脉高压大鼠模型，以评估雷诺嗪是否能降低离体右心房房性心律失常的发生率。给四周龄的Wistar大鼠注射50mg/kg的野百合碱，并在14天后研究离体右心房功能。心脏出现右心房和右心室肥大，心电图显示P波时限和QT间期增加，这些都是该疾病的标志。此外，注射野百合碱导致离体右心房变时性增强，收缩和舒张动力学加快。另外，雷诺嗪对离体右心房呈现出浓度依赖性的变时性和变力性作用，与实验模型相比，在对照组中效力更高。采用猝发起搏方案时，来自野百合碱处理动物的离体右心房更容易发生心律失常，而雷诺嗪能够减轻这种表型。因此，我们得出结论，野百合碱诱导的肺动脉高压大鼠模型出现了右心房重构，这增加了发生离体房性心律失常的易感性，而抗心律失常药物雷诺嗪改善了这种表型。
