Atrial Fibrillation Induced Atrial Acute Electrical Rmodeling: Correlation With Cardiac Autonomic Nervous System

Atrial fibrillation (AF) is one of the most popular cardiac arrhythmias in heart disease, but the mechanisms underlying AF have not been well elucidated. In1950, Scherf D Found used acetylcholine at the sinus node or atrioventricular node was the most effective sites to induce atrial fibrillation, so they concluded the opinion of focal trigger AF. In1997and1998, Jais and Haissaguerre's found the firing in the pulmonary veins correlated to the initiation of AF in paroxysmal AF patients. Their research testified the idea of focal trigger AF. But the focal trigger is not act alone, it is affected by many factors. Panpone et al found vagal reflexes in the procedure of circumferential pulmonary vein ablation enhances long-term benefit after circumferential ablation for paroxysmal.atrial fibrillation, their research indicate autonomic factors may play a role in the initiation and maintenance of AF.Guodeng Niu et al research found GP ablation can shorten acetylcholine induced AF duration. This research showed the intrinsic cardiac nerve system may be one of the AF maintenance factors. Zhibing Lu et al showed HFS caused atrial acute remodeling, HFS cause ERP decreased, WOV increased and AF threshold decreased;GP ablation can inhibit and reverse this atrial acute electrical remodeling, they concluded the atrial acute remolding is related to the hyperactive GP. Xia et al found Low-level vagosympathetic nerve stimulation (LL-VNS) may prevent episodic AF due to rapid PV and non-PV firing and LL-VNS can prevent and reverse atrial remodeling induced by RAP.In2004, Pachon et al. coined the term "AF nests" to describe the electrical properties of a unique type of electrogram seen during sinus rhythm in patients with atrial fibrillation (AF). Ablation directed at the "AF nests" was associated with successful freedom from AF recurrence with and without the use of anti-arrhythmic drugs. In2004, Nademanee et al.(3) found that ablation of low-level, complex fractionated atrial electrograms (CFAE) during AF was also associated with a higher success rate for patients with drug resistant AF. In2007, Gregory M Marcus, they found Regional differences in voltage are present in patients with atrial arrhythmias, with AF patients exhibiting significantly more low-voltage areas in the septum and posterior walls in sinus rhythm. In2007, Nicolas Lellouche et al found a specific pattern of pre-ablation sinus rhythm EGM (deflections≥4, amplitude≥0.7mV, and duration≥40ms) was strongly associated with parasympathetic responses, Local acetylcholine release could potentially explain this phenomenon.The sinus rhythm is stable, to find the atrial fibrillation substrate in sinus rhythm is meaningful.The mechanism (s) underlying'AF nest', or broadly speaking the AF substrate during sinus rhythm, has not been elucidated. Furthermore, identification of the'AF nest'is limited by the requirement of custom made software to detect the high frequency component of the fibrillatory myocardium during SR. It has been suggested that anisotropy, short refractoriness, heterogeneous areas of stretch and fibrosis, as well as autonomic factors may play a role in the creation of'AF nests'. Arruda and Natale have speculated that these highly resonant sites (AF nests) may harbor CFAE during AF. The present study was intended to identify the AF substrate in sinus rhythm and correlate their anatomic and functional relationship to the areas exhibiting CFAE during AF. We utilized an AF model of rapid atrial pacing in which a non-contact mapping array was employed to quantitate the low voltage area, another hallmark of the'AF nest', before and after rapid atrial pacing (RAP). Furthermore, we ablated the major ganglionated plexi (GP) prior to RAP or LL-VNS to determine the influence of the intrinsic cardiac autonomic nervous system and extrinsic cardiac Autonomic nervous system on these AF substrates as well as the development of CFAE. Part1GP ablation inhibit the atrial acute electrical remodeling induced by AF:evidence from non-contact mapping system.Introduction:The mechanism (s) underlying'AF nest', or broadly speaking the AF substrate during sinus rhythm, has not been elucidated.Objective:The present study was intended to identify the AF substrate in sinus rhythm and correlate their anatomic and functional relationship to the areas exhibiting CFAE during AF. Furthermore, we ablated the major ganglionated plexi (GP) prior to RAP to determine the influence of the intrinsic cardiac autonomic nervous system on these AF substrates as well as the development of CFAE.Methods:22dogs were divided into2groups. Group1(n=15) received3hours RAP without GP ablation. Group2(n=7), ablate the GP at baseline,then received3hours RAP without GP ablation. All dogs were anesthetized with Na-pentobarbital,50mg/kg, and ventilated with room air by a positive pressure respirator at20times/min. left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins (PV) and atrial appendages (AA). RAP was used to induce AF for3hours while mapping with a non-contact array in the right atrium in each animals. Group-1(n=15):Programmed stimulation (PS) was performed at baseline and during3-hour RAP. PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). Group-2(n=7):After baseline ERP and WOV determinations, Prior to RAP for3hours, the superior left GP, inferior left GP,anterior right GP,inferior right GP and LOM were ablated. Then3-hour concomitant RAP was applied. After each hour of RAP, the ERP and WOV for AF were measured at each PV and AA site during SR. We reconstruct a3D geometry of the right atrial. In both group, we record a episode of SR electrograms and atrial fibrillation electrograms at baseline, lhour,2hour,3hour RAP. We performed voltage mapping of right atrial by DSM(absolute), define the voltage≤0.5mV as low-voltage area(LVA) and the voltage≥1.5mV as normal voltage area(NVA) in sinus rhythm and CFAE and normal voltage area(NVA) in atrial fibrillation. We also Measure the cycle length of SR at baseline, at the end of1h,2h and3h RAP and atrial fibrillation cycle length.Results:In group1, the ERP decreased significantly at left PV sites, right PV sites and left atrial appendage; whereas the ΣWOV increased significantly from14.13±5.58ms at baseline to120.13±9.78ms after3hours RAP (p<0.001, n=15). In group2(n=7), After GP ablation, the ERP andΣOV showed no significant change with3hours of RAP induced AF. In group1, the low-voltage area(LVA) increased significantly from0.21±0.09CM2at baseline to2.62±0.58CM2after3hours RAP.(p<0.001, n=15). The LVA mainly located at the posterior wall, lateral wall and anterior wall of right atrial and septum of right atrial. And the normal voltage area (NVA) decreased significant from56.39±4.84CM2at baseline to45.5±4.79CM2after3hours RAP in group1(p<0.001, n=15), even after1hour RAP,the NVA decreased significant (from56.39±4.84CM2to48.79±4.36CM2, p<0.01).In group1, the CFAE area increased significant after3h RAP than1h RAP(34.5±5.075VS24.52±3.780, p<0.001), the NVA decreased at the end of3h RAP than1h RAP, but no significant change.At least one of the LVA developed into CFAE area in AF. In group2. After GP ablation, the LVA (from1.37±0.71CM2at baseline to1.00±0.32CM2at the end of3hours RAP, P=NS) and NVA (from48.14±4.99CM2at baseline to38.24±5.12CM2at the end of3hours RAP, P=NS) showed no significant change with3hours of RAP induced AF. In goup2, the CFAE area and NVA at the end of3h RAP had no significant change compared with at the end pf1h RAP. In both group1and group2, the heart rate in sinus rhythm (SR) and AF cycle length had no significant change during3hours RAP induced AF(P=NS).Conclusions:These findings suggest a direct connection between low iso-potential areas in SR and CFAE during AF based on underlying GP activity. Part2Prevention atrial fibrillation induced atrial acute electrical remodeling by low level vagosympathetic nerve stimulation.Introduction:Recently some studies showed that low level vagosympathetic nerve stimulation (LL-VNS) can be anti-arrhythmogenic.Objective:We hypothesized low level vagosympathetic nerve stimulation (LL-VNS) can prevent atrial fibrillation induced atrial acute electrical remodeling:insight from non-contact mapping system.Methods:16dogs were divided into2groups. Group1(n=8) received3hours RAP without LL-VNS. Group2(n=8), received3hours RAP and LL-VNS at the same time electrical stimulation (20Hz) applied to right vagosympathetic trunk at voltages50%below the threshold which slowed sinus rate or AV conduction. All dogs were anesthetized with Na-pentobarbital,50mg/kg, and ventilated with room air by a positive pressure respirator at20times/min. left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins (PV) and atrial appendages (AA). RAP was used to induce AF for3hours while mapping with a non-contact array in the right atrium in each animals. Right vagosympathetic trunk were separated and2silk electrodes were inserted into the vagosympathetic trunk in all dogs. In both groups: Programmed stimulation (PS) was performed at baseline and during3-hour RAP. PS allowed determination of ERP and AF inducibility measured by WOV. We reconstruct a3D geometry of the right atrial. In both group, we record a episode of SR electrograms and atrial fibrillation electrograms at baseline,1hour,2hour,3hour RAP. We performed voltage mapping of right atrial by DSM(absolute), define the voltage≤0.5mV as low-voltage area(LVA) and the voltage≥1.5mV as normal voltage area(NVA) in sinus rhythm and CFAE and normal voltage area(NVA) in atrial fibrillation. We also Measure the cycle length of SR at baseline, at the end of1h,2h and3h RAP and atrial fibrillation cycle length.Results:In group1, the ERP decreased significantly at LSPV, RSPV, RIPV, RAA and LAA. The ERP had no significantly at LIPV site, but the trend toward a decrease in ERP was consistently seen. In group2, the ERP had no significantly decreased at all atrial appendages and PV sites. In group1, the ΣWOV increased significantly from55.00±18.20ms at baseline to165.5±31.16ms after3hours RAP (p<0.01, n=8). In group2, the ΣWOV showed no significant change with3hrs of RAP induced AF.(from28.25±8.19at baseline to28.50±6.13after3hours RAP, p=NS, n=8). In group1, the low-voltage area (LVA) increased significantly from0.14±0.12CM2at baseline to2.4±0.89CM2after3hours RAP (P<0.01), but the normal voltage area (NVA) decreased significant from55.85±3.36CM2at baseline to44.60±4.04CM2after3hours RAP (p<0.001, n=8). In group1, the CFAE area increased significant after3h RAP than1h RAP (36.29±6.294VS26.81±5.076, p<0.05), the NVA during AF decreased at the end of3h RAP than1h RAP(10.31±1.856VS6.588±1.839, p>0.05), but no significant change.In group2, the LVA (from0.79±0.29CM2at baseline to1.18±0.77CM2at the end of3hours RAP, P=NS) and NVA (from44.11±2.98CM2at baseline to40.85±2.32CM2at the end of3hours RAP, P=NS) showed no significant change with3hrs of RAP induced AF. In goup2, the CFAE area and NVA at the end of3h RAP had no significant change compared with at the end pf1h RAP. In both group1and group2, the heart rate in sinus rhythm (SR) and AF CYCLE LENGTH had no significant change during3hours RAP induced AF(P=NS).Conclusion:LL-VNS prevent atrial fibrillation induced atrial acute electrical remodeling. Inhibition of the intrinsic cardiac autonomic nervous system may be responsible for this effect...