Murphy Matthew B, Kim Kyungsoo, Kannankeril Prince J, Murray Katherine T
Departments of Medicine, Pediatrics and Pharmacology, Vanderbilt University School of Medicine.
Departments of Medicine, Pediatrics and Pharmacology, Vanderbilt University School of Medicine;
J Vis Exp. 2022 Jun 29(184). doi: 10.3791/64168.
Mouse models of genetic and acquired risk factors for atrial fibrillation (AF) have proven valuable in investigating the molecular determinants of AF. Programmed electrical stimulation can be performed using transesophageal atrial pacing as a survival procedure, thus enabling serial testing in the same animal. However, numerous pacing protocols exist, which complicates the reproducibility. The present protocol aims to provide a standardized strategy to develop model-specific experimental parameters to improve reproducibility between studies. Preliminary studies are performed to optimize the experimental methods for the specific model under investigation, including age at the time of the study, sex, and parameters of the pacing protocol (e.g., mode of pacing and definition of AF susceptibility). Importantly, care is taken to avoid high stimulus energies, as this can cause stimulation of the ganglionic plexi with inadvertent parasympathetic activation, manifested by exaggerated atrioventricular (AV) block during pacing and often associated with artifactual AF induction. Animals demonstrating this complication must be excluded from the analysis.
心房颤动(AF)遗传和后天危险因素的小鼠模型已被证明在研究AF的分子决定因素方面具有重要价值。使用经食管心房起搏作为一种存活程序可以进行程控电刺激,从而能够在同一只动物身上进行系列测试。然而,存在许多起搏方案,这使得可重复性变得复杂。本方案旨在提供一种标准化策略,以制定特定模型的实验参数,从而提高研究之间的可重复性。进行初步研究以优化针对所研究特定模型的实验方法,包括研究时的年龄、性别以及起搏方案的参数(例如,起搏模式和AF易感性的定义)。重要的是,要注意避免高刺激能量,因为这可能会导致神经节丛受到刺激并意外激活副交感神经,表现为起搏期间房室(AV)阻滞过度,并且常常与人为诱导的AF相关。出现这种并发症的动物必须排除在分析之外。