Autonomic mechanism for chronic atrial electrical remodeling induced by rapid atrial pacing in ambulatory danines

Objetives The mechanism for changes in the electrophysiological properties of the atria during rapid pacing induced atrial fibrillation(AF) is not well understood.We aimed to investigate the contribution of intrinsic cardiac autonomic nervous system(ICANS) in chronic atrial electrical remodeling and AF induced by rapid atrial pacing for 4 weeks. Methods Twelve adult mongrel dogs weighing 15 to 20 kg were assigned to two groups;group 1(experimental group,n= 7) and group 2(control group,n =5).All dogs were anesthetized with propofol and mechanically ventilated via endotracheal tubes.The chest was entered via bilateral mini-thoracotomy at the fourth intercostals space.Bipolar pacing electrode was sutured to the right atrial appendage.Four-electrode catheters(Biosense-Webster,Diamond Bar,CA) were secured to allow recording at the right and left atriaum.All tracings from the electrode catheters were amplified and digitally recorded using a computer-based Bard Laboratory System (CR Bard Inc,Billerica,MA).Electrograms were filtered at 50 to 500 Hz.Continuous rapid pacing(600 bpm, 2×threshold[TH]) was performed at the right atrial appendage. Ganglionated Plexi(GP) was localized by applying high frequency stimulation(HFS;20 Hz,0.1ms duration, 0.5 to 4.5 V)with a bipolar stimulation-ablation probe electrode (AtriCure,West Chester,OH).Group1 underwent ablation of bilateral GP and ligament of Marshall followed by 4-week pacing.Group 2 underwent sham operaton without ablation of GP and ligament of Marshall followed by 4-week pacing.The effective refractory period(ERP) and window of vulnerability(WOV) were measured at 2×TH before(baseline) and every week after GP ablation.WOV was defined as the difference between the longest and the shortest coupling interval of the premature stimulus that induced AF.GP consist of the anterior right ganglionated plexi(ARGP) located in the fat pad at the right superior pulmonary vein(RSPV)-atrial junction;the inferior right ganglionated plexi(IRGP) located at the inferior vena cava/right atrial junction;the superior left ganglionated plexi(SLGP) at the left superior pulmonary vein(LSPV) /left atrial junction and the inferior left ganglionated plexi(ILGP) at the left inferior pulmonary vein (LIPV)/left atrial junction.Results Immediately after ablation, the ERP in Group 1 became markedly longer and started to shorten gradually during the first 2 weeks,then stabilized at the 4th week.Compared to Group2,the ERP of Group1 was significantly longer in the first 3 weeks(P【 0.05),but no obvious difference at the 4th week in either the right or left atrium(P】0.05).In Group 1,AF could not be induced(WOV=0)in the first 3 weeks after ablation, and at the 4th week,AF was induced in 2 of 7 dogs.In Group2,WOV progressively widened during the 4-week period. AF could not be induced in 5 of 7 dogs in Group 1 and 1 of 5 dogs in Group 2 during the 4-week pacing period. Conclusions The intrinsic cardiac autonomic nervous system (ICANS) plays an important role in the early stage of atrial electrical remodeling induced by rapid atrial pacing.On the other hand,with time passing by,its effect on the formation of AF decreases gradually,which suggests that ICANS may account for a non-dominant factor in the late stage of the rapid pacing-induced chronic atrial fibrillation.