Abstract
Complete atrioventricular block (CAVB) is a largely intractable disease that leads to severe bradyarrhythmia. The only treatment is the implantation of a pacemaker device. Left untreated, CAVB patients experience QT prolongation and ventricular overload, increasing susceptibility to cardiac remodeling and heart failure, as well as potentially lethal tachyarrhythmias. Animal models of CAVB offer a direct avenue to investigate the disease and potential disease-modifying therapies. However, existing models have limitations due to phenotype instability and high attrition rate. We aimed to create an improved method for disease model creation and report beating rate and variability analysis of the model. We report a modified surgical model of CAVB in rats by adapting a clinical radiofrequency energy generator to ablate the atrioventricular node region of the rat heart. Compared to previous ablation methods that utilize sharp needle entry into the AV node (AVN) region, the modified method resulted in a significantly higher success rate with a lower attrition rate. The rat model of CAVB showed stable conduction block for at least four weeks after model creation, supporting their suitability as a preclinical model of severe bradyarrhythmia due to AV conduction block. Models showed severe beat-to-beat variability with decreased overall autonomic innervation. We present a rodent model of a complete and stable AV block, which enhances the rigor and reproducibility of the disease model and downstream applications.