Effect Of Denervation On Acute Atrial Electrical Remodeling And Inducibility Of Atrial Fibrillation

Part I The time course of the effect of the autonomic nerve on acute atrial electrical remodeling and inducibility of atrial fibrillationObjective:The autonomic nerve plays an important role in the initiation and maintenance of atiral fibrillation (AF). Atrial electrical remodeling (AER) is the underlying mechanism of AF. However, the impact of autonomic nerve on AER is unclear. The present study investigated the time course of the effect of the autonomic nerve on acute AER (AAER) and inducibility of AF.Methods:14 mongrel dogs were involved. All dogs were anesthetized with sodium pentobarbital. Bilateral cervical vagosympathetic trunks were decentralized by surgical procedures for vagosympathetic nerve stimulation (VNS). The chest was opened. The pericardium was cut open and sewn to the chest wall to cradle the heart. AAER was performed through 4-h rapid atrial pacing (RAP). The atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured with and without bilateral cervical vagosympathetic nerve stimulation (VNS) at the high right atrium (HRA), ostium of the coronary sinus (CSO) and distal coronary sinus (CSD) before and after every hour of RAP.Results:After 1h of RAP, ERP was markedly shortened (123.71±12.62 vs 105±15.06 ms at HRA, P<0.01; 107.71±14.86 vs 94.29±14.53 ms at CSO, P<0.01; 107.71±14.90 vs 90.71±16.85 ms at CSD, P<0.01), reached the minimum (97.86±32.62 ms at HRA,93.07±9.35 ms at CSO,90.0±16.17 ms at CSD) after 2 h of RAP, and then stabilized. After RAP, only one dog could be induced at CSD (after 1 h of RAP, VW 10 ms; 2h, VW 20 ms; 3 h, VW 10 ms; 4 h, VW 10 ms). Before RAP, ERP was significantly shortened under VNS (HRA,123.71±12.62 vs 72.14±23.92 ms, P<0.01; CSO, 107.71±14.86 vs 73.57±26.20 ms, P<0.01；CSD,107.71±14.90 vs 69.29±24.64 ms, P<0.01). AF was easily induced with VNS. The change of VW between before and after RAP was slight.AF was only slightly induced. VNS significantly shortened ERP and increased VW before and after RAP. Compared with ERP under VNS before RAP, after 1 h of RAP, ERP under VNS was significantly shortened (72.14±23.92 vs 58.57±29.05 ms at HRA, P<0.05; 73.57±26.20 vs 53.57±20.98ms at CSO, P<0.05; 69.29±24.64 vs 46.43±20.03ms at CSD, P<0.05), reached the minimum (55.0±24.42 ms at HRA,51.43±22.48 ms at CSO,45.71±20.27 ms at CSD) after 2 h of RAP, and then stabilized. The change of VW under VNS between before and after RAP was slight. The time course of RAP and VNS on AAER was similar. No difference in the ERP and VW at the different sites with or without VNS were observed (P>0.05).Conclusions:RAP resulted in AAER, which may be mediated and aggravated by autonomic activity. The time course of RAP and VNS on AAER was similar.Part II Effect of Denervation on acute atrial electrical remodeling and inducibility of atrial fibrillationObjective:Atrial electrical remodeling (AER) is the underlying mechanism of AF. The autonomic nerve plays an important role in the initiation and maintenance of atrial fibrillation (AF). Both endocardial intervention and ablation of epicardial ganglionated plexuses could cause denervation and improve the success rate of AF ablation. However, the mechanism of this is not well understood, and there is controversy surrounding the above results. The present study investigated the effect of epicardial fat pad (FP) ablation on acute AER (AAER) and inducibility of AF.Methods:14 dogs (ablation group) were involed. Bilateral cervical vagosympathetic trunks were decentralized by surgical procedures for vagosympathetic nerve stimulation (VNS). All dogs were anesthetized with sodium pentobarbital. The chest was opened. The pericardium was cut open and sewn to the chest wall to cradle the heart for epicardial FP ablation. Then, all dogs underwent 4-h rapid atrial pacing (RAP). The atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured with and without bilateral cervical vagosympathetic nerve stimulation (VNS) at the high right atrium, ostium of the coronary sinus (CS) and distal CS, before and after every hour of RAP.Results:ERP was significantly prolonged after FP ablation (without VNS:125.0±18.29 vs 142.14±17.62 ms at HRA, P<0.01; 106.43±16.92 vs 122.14±20.07 ms at CSO, P<0.01; 105.0±16.53 vs 119.29±15.42 ms at CSD, P<0.01; with VNS:72.86±15.41 vs 138.57±25.38 ms at HRA, P<0.01; 67.14±26.14 vs 115.71±21.74 ms at CSO, P<0.01; 65.71±19.10 vs 113.57±25.90 ms at CSD, P<0.01). Moreover, neither VNS nor RAP shortened the ERP (after 1 h of RAP:without VNS, HRA,145.0±20.29 ms, CSO,124.29±22.09 ms, CSD,122.86±21.99 ms, with VNS, HRA,147.14±22.34 ms, CSO, 122.86±24.31 ms, CSD,127.14±25.55 ms; after 2 h of RAP:without VNS, HRA,146.43±23.73 ms, CSO,126.43±23.73 ms, CSD,132.86±19.78 ms, with VNS, HRA,147.14±20.91 ms, CSO,129.29±24.33 ms, CSD,132.14±18.47 ms; after 3 h of RAP:without VNS, HRA,146.43±21.34 ms, CSO, 127.86±28.33 ms, CSD,133.57±22.05 ms, with VNS, HRA,149.29±18.17 ms, CSO,130.0±27.46 ms, CSD,139.29±24.95 ms; after 4 h of RAP: without VNS, HRA,149.29±19.79 ms; CSO,129.29±26.45 ms; CSD, 135.71±22.09 ms, with VNS, HRA,150.0±17.10 ms, CSO,132.14±26.94 ms; CSD,136.43±23.73 ms) or increased the VW (VW=0). AF could not be induced (VW=0). Conclusions:Epicardial FP ablation generated denervation and prolonged atiral ERP. Both RAP and VNS could not shorten ERP or increase VW, which not only abolishes AF inducibility but also prevents RAP-mediated AAER.Part III Effect of Denervation on the Long-term Efficacy of Circumferential Pulmonary Vein Ablation of Paroxysmal Atrial FibrillationObjective:Circumferential pulmonary vein ablation (CPVA) is an important therapy for atrial fibrillation (AF). Autonomic nerve denervation involves in the mechanism of AF ablation. However, the relationship between autonomic nerve denervation and long-term efficacy of CPVA has not been well understood.Methods:106 consecutive paroxysmal AF(PAF) patients with symptomatic and drug refractory AF (Male 69. age 59.80±10.57 yrs) were enrolled in this study. All patients underwent CPVA. During follow-up,24 hour Holter monitoring was performed before and after procedure. Then the patients accepted Holter examination every 3 to 6 months. Free of atrial tachyarrhythmias (>30 sec) during follow-up was regarded as no recurrence. Autonomic nerve denervation was assessed by heart rate variability (HRV) from Holter.Results:102 patients finished the study. Each patient underwent 1.31±0.50 procedures. Mean follow-up was 32.73±12.96 months. According to the outcome, the involved patients were divided into two groups. Success group:79 patients were free of AF without antiarrhythmias drugs. Recurrence group:23 patients had recurrent AF. The overall cumulative success rate was 77.5%. Before ablation, HRV characters of Success group were comparable to Recurrence Group. After CPVA, HRV decreased significantly in each group (Success group:SDNN 143.82±50.07 vs 97.13±51.36, SDANN 204.63±90.96 vs 161.76±89.32, rMSSD 82.74±60.46 vs 61.85±55.47, PNN50 16.71±18.98 vs 10.89±15.50,CV 0.086±0.049 vs 0.063±0.048, TF 11038.69±8818.7 vs 5553.15±6443.40, ULF 6313.15±5023.95 vs 3638.78±5594.66, VLF 3061.84±4870.91 vs 1006.00±1345.81, LF 780.00±1285.99 vs 314.80±555.01, LF/HF 0.88±0.89 vs 0.74±0.61, P< 0.01; HF 882.21±1441.98 vs 529.95±1014.48, P< 0.05. Recurrence group: SDNN 167.02±57.41 vs 124.57±57.95, SDANN 248.58±298.96 vs 184.81±82.14, rMSSD 113.98±88.33 vs 85.53±66.42, PNN5027.72±27.01 vs 18.34±20.68, CV 0.251±0.9525 vs 0.093±0.082, TF 14107.61±9938.46 vs 8774.57±8013.03, VLF 3519.71±3238.26 vs 1575.44±1578.55, LF 1339.85±1953.36 vs 602.42±895.80, LF/HF 1.13±0.71 vs 0.70±0.38, P< 0.01; ULF 7655.10±6637.86 vs 5552.92±6636.34, HF 1792.94±2596.30 vs 1025.71±1547.95, P<0.05。Furthermore, the characters of SDNN, rMSSD, PNN50, CV, TF, ULF, VLF, LF and HF of Success group were significantly lower than those of Group Recurrence(P<0.05).Conclusions:CPVA is an effective therapy for PAF. CPVA could induce autonomic nerve denervation, which may contribute to the long-term success of AF ablation.