The Experimental Study Of Mechanism Of Atrial Tachycardia After FONTAN Operation

Objective:To explore the mechanism of atrial tachycardia after Fontan operation in canine model.Methods:The Fontan canine model was created by connecting right atrial appendage and pulmonary artery with a GORE-TEX conduit and ligating the proximal pulmonary artery.Dogs were observed seven days after operation and subjected to open-chest study,in vitro optical mapping,and/or cell isolation for perforated whole cell patch-clamp to investigate the right atrial electrophysiology.Ionic remodeling was studied by RT PCR,Western-Blot and whole cell patch-clamp.Calcium transient and Ca²⁺spontaneous release event were detected with video-based motion edge-detection system?IonOptix,USA?.Results:Five dogs survived from Fontan operation.Dilatation of right atrium was observed?13.90±1.25mm pre-operation versus 17.08±1.73mm 7 days after operation,p<0.01?,and pressure?8.40±1.14mmHg pre-operation versus 17.80±2.39mmHg 7days after operation,p<0.01?as well.Electrophysiology study showed atrial tachycardia was easy to be induced by burst pacing in model dogs,and effective refractory periods?ERP?and action potential duration?APD?were shortened.The impulse conduction velocity was decreased compared to control group,and conduction phase heterogeneity was increased.The whole cell patch-clamp recording demonstrated I_to and I_CaL reduction,while I_K1,I_f and I_NCX enlargement.The relative mRNA and protein expression changed likewise.Ca²⁺imaging indicated increased diastolic calcium level?131.27±30.63 nmol/L in model group versus 98.46±21.98nmol/L in control group,p<0.01?and decreased calcium transient amplitude?46.66±13.41 nmol/L in model group versus 86.36±22.51 nmol/L in control group,p<0.01?.Triggered activity was increased in model group.Conclusions:1.The Fontan canine model by connecting right atrial appendage and pulmonary artery with a GORE-TEX conduit,and partly blocking the blood flow of pulmonary artery can survive for a long time?more than 1 week?,and the procedure can lead to increased right atrial pressure,right atrial dilatation and increased atrial fibrosis.2.Shortened ERP and APD,slow conduction and increased heterogeneity,ectopic activity of right atrium may promote atrial tachycardia initiation and maintenance after Fontan operation.3.Shortened repolarization resulting from decreased I_to,I_CaL and increased I_K1 may precede the occurrence of atrial tachycardia after Fontan operation.4.Calcium handling abnormality may play a role in the mechanism of atrial tachycardia after Fontan operation.5.Increased I_f may promote atrial tachycardia after Fontan operation.