A highly effective, rodent model of complete heart block by epicardial radiofrequency ablation
Alexander N Weltz1,2, Lea Fortuno-Miranda1,2, Aravindan Kolandaivelu3
1The Blalock-Taussig-Thomas Pediatric and Congenital Heart Center, The Johns Hopkins Children's Center, Baltimore, MD, 21224, USA.
Insights
Researchers developed a new, more successful rat model for complete atrioventricular block (CAVB), a heart rhythm disorder. This stable preclinical model aids in studying severe bradyarrhythmia and developing new therapies.
Area of Science:
- Cardiovascular Research
- Animal Models
- Electrophysiology
Background:
- Complete atrioventricular block (CAVB) causes severe bradyarrhythmia, necessitating pacemaker implantation.
- Untreated CAVB leads to QT prolongation, ventricular overload, heart failure, and tachyarrhythmias.
- Existing animal models for CAVB have limitations including phenotype instability and high attrition rates.
Purpose of the Study:
- To develop an improved and stable rodent model for studying complete atrioventricular block (CAVB).
- To analyze the beating rate and variability in the newly created CAVB rat model.
- To enhance the rigor and reproducibility of CAVB disease modeling for preclinical research.
Main Methods:
- A modified surgical technique using a clinical radiofrequency energy generator to ablate the atrioventricular node region in rats.
- Comparison of the modified ablation method with previous sharp needle entry techniques.
- Assessment of conduction block stability over four weeks and analysis of beat-to-beat variability and autonomic innervation.
Main Results:
- The modified radiofrequency ablation method demonstrated a significantly higher success rate and lower attrition rate compared to prior methods.
- The created rat model exhibited stable complete atrioventricular block for at least four weeks.
- The model displayed severe beat-to-beat variability and reduced overall autonomic innervation, consistent with CAVB.
Conclusions:
- This study presents a novel, stable, and reproducible rodent model for complete atrioventricular block.
- The enhanced model overcomes limitations of previous CAVB models, improving preclinical research.
- This model facilitates the investigation of disease-modifying therapies for severe bradyarrhythmia.
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.
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