Development of an Ovine Model of Pediatric Complete Heart Block

Abstract

Complete heart block is a significant clinical problem that can limit the quality of life in affected children. To understand the pathophysiology of this condition and provide for development of novel therapies, we sought to establish a large animal model of permanent, pacemaker-dependent atrioventricular block (AVB) that mimics the size and growth characteristics of pediatric patients. We utilized nine immature lambs weighing 10.5 ± 1.4 kg. After implantation of dual-chamber pacemaker devices with fixed leads, AVB was produced by interrupting His-bundle conduction using radio-frequency ablation at the base of the non-coronary cusp of the aortic valve. Ablations (30 to 60 s in duration) were performed under fluoroscopic guidance with electrophysiological monitoring. Interrogation of pacemakers and electrocardiography (ECG) determined the persistence of heart block. Ovine hearts were also examined immunohistochemically for localization of conduction tissue. AVB was produced in eight animals using an atypical approach from the left side of the heart. One animal died due to ventricular fibrillation during ablation proximal to the tricuspid annulus and one lamb was sacrificed postoperatively due to stroke. Four sheep were kept for long-term follow-up (109.8 ± 32.9 d) and required continuous ventricular pacing attributable to lasting AVB, despite significant increases in body weight and size. We have created a large animal model of pediatric complete heart block that is stable and technically practicable. We anticipate that this lamb model will allow for advancement of cell-based and other innovative treatments to repair complete heart block in children.