IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Pessac, France (V.D., D.B., F.R., S.H.G., M.C., S.C., D.E., B.Q., H.C., M.H., C.R., P.B., J.-B.T., O.B.).
Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, France. (V.D., D.B., F.R., S.H.G., M.C., S.C., D.E., B.Q., H.C., M.H., P.B., J.-B.T., O.B.).
Circ Arrhythm Electrophysiol. 2018 Oct;11(10):e006059. doi: 10.1161/CIRCEP.117.006059.
Ventricular arrhythmias are frequent in patients with repaired tetralogy of Fallot (rTOF), but their origin and underlying mechanisms remain unclear. In this study, the involvement of left ventricular (LV) electrical and structural remodeling was assessed in an animal model mimicking rTOF sequelae.
Piglets underwent a tetralogy of Fallot repair-like surgery (n=6) or were sham operated (Sham, n=5). Twenty-three weeks post-surgery, cardiac function was assessed in vivo by magnetic resonance imaging. Electrophysiological properties were characterized by optical mapping. LV fibrosis and connexin-43 localization were assessed on histological sections and protein expression assessed by Western Blot.
Right ventricular dysfunction was evident, whereas LV function remained unaltered in rTOF pigs. Optical mapping showed longer action potential duration on the rTOF LV epicardium and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction in rTOF LVs but not in the transverse direction compared with Sham. An elevated collagen content was found in LV basal and apical sections from rTOF pigs. Moreover, a trend for connexin-43 lateralization with no change in protein expression was found in the LV of rTOFs. Finally, rTOF LVs had a lower threshold for arrhythmia induction using incremental pacing protocols.
We found an arrhythmogenic substrate with prolonged heterogeneous action potential duration and reduced conduction velocity in the LV of rTOF pigs. This remodeling precedes LV dysfunction and is likely to contribute to ventricular arrhythmias and sudden cardiac death in patients with rTOF.
修复性法洛四联症（rTOF）患者常发生室性心律失常，但心律失常的起源和潜在机制仍不清楚。在本研究中，通过模拟 rTOF 后遗症的动物模型评估了左心室（LV）电重构和结构重构的参与情况。
小猪接受了法洛四联症修复样手术（n=6）或假手术（Sham，n=5）。手术后 23 周，通过磁共振成像进行体内心功能评估。通过光学映射对电生理特性进行了特征描述。在组织切片上评估 LV 纤维化和连接蛋白 43 定位，并通过 Western Blot 评估蛋白表达。
右心室功能障碍明显，而 rTOF 猪的 LV 功能保持不变。光学映射显示 rTOF LV 心外膜和心内膜的动作电位持续时间较长。rTOF LV 的纵向方向上的心外膜传导速度明显降低，但与 Sham 相比，横向方向上没有变化。rTOF 猪的 LV 基底和心尖节段胶原含量升高。此外，在 rTOF 的 LV 中发现了连接蛋白 43 侧化的趋势，但蛋白表达没有变化。最后，使用递增起搏方案，rTOF 的 LV 诱发心律失常的阈值较低。
我们发现 rTOF 猪的 LV 存在致心律失常基质，表现为动作电位持续时间延长和传导速度降低。这种重构发生在 LV 功能障碍之前，可能导致 rTOF 患者发生室性心律失常和心脏性猝死。
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