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A rat model of complete atrioventricular block recapitulates clinical indices of bradycardia and provides a platform to test disease-modifying therapies

Authors
 Nam Kyun Kim  ;  David Wolfson  ;  Natasha Fernandez  ;  Minji Shin  ;  Hee Cheol Cho 
Citation
 Scientific reports, Vol.9(1) : 6930, 2019-05 
Journal Title
 Scientific reports 
Issue Date
2019-05
MeSH
Animals ; Atrioventricular Block / diagnosis ; Atrioventricular Block / mortality ; Atrioventricular Block / physiopathology* ; Atrioventricular Block / therapy* ; Biopsy ; Bradycardia / diagnosis ; Bradycardia / mortality ; Bradycardia / physiopathology* ; Bradycardia / therapy* ; Catheter Ablation / methods ; Combined Modality Therapy ; Disease Management ; Disease Models, Animal ; Echocardiography ; Electrocardiography ; Female ; Heart Rate ; Immunohistochemistry ; Male ; Rats ; Time Factors ; Ventricular Remodeling
Abstract
Complete atrioventricular block (CAVB) is a life-threatening arrhythmia. A small animal model of chronic CAVB that properly reflects clinical indices of bradycardia would accelerate the understanding of disease progression and pathophysiology, and the development of therapeutic strategies. We sought to develop a surgical model of CAVB in adult rats, which could recapitulate structural remodeling and arrhythmogenicity expected in chronic CAVB. Upon right thoracotomy, we delivered electrosurgical energy subepicardially via a thin needle into the atrioventricular node (AVN) region of adult rats to create complete AV block. The chronic CAVB animals developed dilated and hypertrophied ventricles with preserved systolic functions due to compensatory hemodynamic remodeling. Ventricular tachyarrhythmias, which are difficult to induce in the healthy rodent heart, could be induced upon programmed electrical stimulation in chronic CAVB rats and worsened when combined with β-adrenergic stimulation. Focal somatic gene transfer of TBX18 to the left ventricular apex in the CAVB rats resulted in ectopic ventricular beats within days, achieving a de novo ventricular rate faster than the slow atrioventricular (AV) junctional escape rhythm observed in control CAVB animals. The model offers new opportunities to test therapeutic approaches to treat chronic and severe CAVB which have previously only been testable in large animal models.
Files in This Item:
T999201974.pdf Download
DOI
10.1038/s41598-019-43300-9
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Kyun(김남균) ORCID logo https://orcid.org/0000-0001-6923-230X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/185992
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