Sydney Medical School, The University of Sydney, Australia.
Center for Heart Research, The Westmead Institute for Medical Research, Sydney, Australia.
PLoS One. 2020 Feb 10;15(2):e0229092. doi: 10.1371/journal.pone.0229092. eCollection 2020.
Sheep have been adopted as a pre-clinical large animal for scientific research as they are good models of cardiac anatomy and physiology, and allow for investigation of pathophysiological processes which occur in the large mammalian heart. There is, however, no defined model of atrioventricular block in sheep to allow for pre-clinical assessment of new cardiac treatment options. We therefore aimed to develop an adult sheep model of atrioventricular block with the focus on future novel applications.
We utilized six sheep to undergo two procedures each. The first procedure involved implantation of a single chamber pacemaker into the right ventricular apex, for baseline assessment over four weeks. The second procedure involved creating atrioventricular block by radiofrequency ablation of the His bundle, before holding for a further four weeks. Interrogation of pacemakers and electrocardiograms determined the persistence of atrioventricular block during the follow up period. Pacemakers were inserted, and atrioventricular block created in 6 animals using a conventional approach. One animal died following ablation of the His bundle, due to procedural complications. Four unablated sheep were assessed for baseline data over four weeks and showed 5.53 ± 1.28% pacing reliance. Five sheep were assessed over four weeks following His bundle ablation and showed continuous (98.89 ± 0.81%) ventricular pacing attributable to persistent atrioventricular block, with no major complications.
We have successfully developed, characterized and validated a large animal model of atrioventricular block that is stable and technically feasible in adult sheep. This model will allow for the advancement of novel therapies, including the development of cell and gene-based therapies.
绵羊已被用作临床前大型动物的模型，因为它们是心脏解剖和生理学的良好模型，并且可以研究在大型哺乳动物心脏中发生的病理生理过程。然而，绵羊中没有定义的房室传导阻滞模型，无法对新的心脏治疗选择进行临床前评估。因此，我们旨在开发一种成年绵羊房室传导阻滞模型，重点是未来的新应用。
我们使用六只绵羊进行了两次手术。第一次手术涉及将单个腔起搏器植入右心室心尖部，以进行四周的基线评估。第二次手术涉及通过射频消融希氏束来制造房室传导阻滞，然后再持续四周。起搏器的检测和心电图确定了在随访期间持续存在房室传导阻滞。使用常规方法将起搏器插入并在 6 只动物中创建房室传导阻滞。一只动物在希氏束消融后因程序并发症而死亡。四只未消融的绵羊进行了四周的基线数据评估，显示 5.53±1.28%的起搏依赖。五只绵羊在希氏束消融后评估了四周，显示出持续的（98.89±0.81%）心室起搏，归因于持续的房室传导阻滞，没有重大并发症。
我们成功地开发、表征和验证了一种稳定且在成年绵羊中技术上可行的大型动物房室传导阻滞模型。该模型将允许新疗法的发展，包括细胞和基因疗法的发展。
