房性心动过速（房速）是Fontan术后最常见的并发症。既往针对折返机制的射频消融方法的复发率高，提示折返并不是Fontan术后房速的唯一机制，其他机制可能也很重要。课题组通过前期的研究发现，Fontan术后局灶性房速的发生率约占30%，而局灶性房速的发生与触发机制密切相关。因此，本项目拟通过建立犬Fontan术后房速动物模型，运用三维标测系统标测出与触发机制有关的右房内电生理异常部位，并通过检测这些部位的超极化激活环核苷酸（HCN）门控通道的表达水平，以及运用全细胞膜片钳技术研究其HCN通道蛋白的活化状况以及If电流水平，并最终通过使用HCN/If拮抗剂和体内基因转染技术干扰心肌局部HCN基因表达，以探讨HCN/If对Fontan术后继发房速的影响及其内在分子机制。据此，为提高Fontan术后房速的疗效，确立新的治疗策略和新的药物靶点提供理论依据。

Fontan type operation is the first-line treatment for tricuspidal atresia and single ventricle. Post-operation atrial tachycardia (AT) is a very common complication. The recurrency after catheter ablation of intraatrial reeentry tachycardia is high, suggesting that reentry is not the only mechanism of post-Fontan AT and other mechanism may also be important. In the previous studies of our research group, we did find that the incidence of focal AT is about 30%, which own to triggers activity. Trigger activity is known to relate closely to hyperpolarization and cyclic nucleotide (HCN)-gated channels and its the main inward ionic current (If) of diastolic depolarization. To further examine the relationship between HCN and post-Fontan AT , we plan to establish a canine model post Fontan operation followed with induction of AT by fast atrial pacing, then perform the electrophysiological study and rebuild right atrium using 3D-mapping system (Carto) to decide sites with abnormal electrograms. The expression level of HCN in these different sites will be tested and compared; using the whole-cell patch clamp the activation status HCN channel and If the current level will be examined. By giving HCN / If antagonists and in vivo gene transfer technology to interference myocardial HCN gene expression, we will explore the impact of HCN / If on AT post-Fontan operation and its intrinsic molecular mechanisms. Accordingly, in order to improve the efficacy of the AT post Fontan operation,our study is going to provide a theoretical basis for establishing new therapeutic strategies and new drug targets.