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Development of an ovine model of pediatric complete heart block
Bjoern Sill1, Nathalie Roy, Peter E Hammer
1Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.
Insights
Researchers developed a lamb model for pediatric complete heart block, enabling new therapies for children. This pacemaker-dependent atrioventricular block (AVB) model offers a stable platform for innovative treatment research.
Area of Science:
- Cardiovascular Research
- Pediatric Cardiology
- Animal Models
Background:
- Complete heart block significantly impacts children's quality of life.
- Understanding the pathophysiology of pediatric heart block is crucial for developing new treatments.
Purpose of the Study:
- To establish a large animal model of permanent, pacemaker-dependent atrioventricular block (AVB).
- To create a model that mimics the size and growth characteristics of pediatric patients.
Main Methods:
- Immature lambs underwent dual-chamber pacemaker implantation.
- Atrioventricular block was induced via radio-frequency ablation of the His-bundle.
- Electrophysiological monitoring and electrocardiography confirmed persistent heart block.
Main Results:
- Successful AVB induction in 8 out of 9 lambs.
- Long-term follow-up demonstrated sustained AVB requiring continuous ventricular pacing.
- The model showed stability despite significant growth in the animals.
Conclusions:
- A stable and practicable large animal model for pediatric complete heart block has been created.
- This lamb model is anticipated to advance cell-based and other innovative therapies for pediatric heart block.
Background:
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.
Materials And Methods:
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.
Results:
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.
Conclusions:
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.
