The Mechanism Of Acute Atrial Fibrillation Mediated By Sympathetic Nerve

Objective:1) To bulid the methodology of acute animal model of atrial fibrillation(AF) induced by increased sympathetic nerve activity.2) To show the dynamic changes ofautonomic nervous system acitivity during sympathetic nerve-induced atrial fibrillation.3)To clarify the effect of stellate ganglion stimulation on AF inducibility and maintenance,and its electrical remodeling and neural remodeling mechanism.4) To explore theefficiency of unilateral stellate ganglionectomy in AF treatment. Methods: Sixteen adultmongrel dogs weighing18to25kg were randomly divided into3groups. Control group(n=4) underwent6-hour rapid atial pacing only. RSG group (n=6) underwent6-hour rightstellate ganglion stimulation puls rapid atial pacing. LSG group (n=6) underwent6-hourleft stellate ganglion stimulation puls rapid atial pacing.1) AF inducibility, AF duration,ERP, dERP and ERP rate-adaption in LA, RA and PV sites were measured.2)Sympathetic nerve discharge and cervical vagal trunk discharge were recorded andanalysed by BL-420F signaling system, heart rate variability were recorded and analysedby holter and dynamic electrocardiogram system, plasma norepinephrine and acetyl-choline were assayed with enzyme linked immunosorbent assay.3) The density of TH,ChAT, GAP-43positive nerve in RA and LA were detectd by immunohistochemistrystaining. The mRNA expression level of TH, ChAT, GAP-43in RA and LA tissue weredetectd by RT-PCR. Results:1) RSG stimulation induced a greater change in heart ratethan LSG stimulation (P＜0.05, at6V to18V), whereas LSG stimulation produced agreater change in SBP than RSG stimulation (P＜0.05, at6V to10V). At strongerstimulation strengths (20V), there were no significant differences between the effects ofLSG vs RSG stimulation on either heart rate or SBP.2) We successfully made the acuteanimal model of AF induced by increased sympathetic nerve activity. In RSG group, theinduction rate of AF was significantly increased (P＜0.05), the duration of AF wassignificantly prolonged, compared with baseline and control group in RA sites. However,there was no significant changes in LA and PV sites. In LSG group, the induction rate ofAF was significantly increased (P＜0.05), the duration of AF was significantly prolonged (P＜0.05), compared with baseline and control group in LA and PV sites. However, therewas no significant changes in RA sites.3) Compared with baseline and control group, theSDNN, LF, HF, LF/HF were significantly increased both in RSG group and LSG group (P＜0.05). Both RSG and LSG stimulation produced greater and much more sympatheticand vagal nervous discharge than control group (P＜0.05), and the sympathetic nervousdischarge showed stronger and earlier than vagal nervous discharge (P＜0.05). Theplasma norepinephrine and acetylcholine level were significantly increased in RSG groupand LSG group than control group (P＜0.05).4) In RSG group, ERP was significantlyshortened (P＜0.05), dERP was significantly increased (P＜0.05), ERP rate-adaption wassignificantly decreased in RA sites (P＜0.05). However, there was no significant changesin LA and PV sites in RSG group. ERP was significantly shortened (P＜0.05), dERP wassignificantly increased (P＜0.05), ERP rate-adaption was significantly decreased in LAand PV sites in LSG group (P＜0.05). However, there was no significant changes in RAsites in LSG group.5) In LA tissues，LSG stimulation produced greater increase of thedensity of TH, ChAT, GAP-43positive nerve and higher level of mRNA expression TH,ChAT, GAP-43than both no SG stimulation and RSG stimulation(P＜0.05). In RAtissues，RSG stimulation produced greater increase of the density of TH, ChAT, GAP-43positive nerve and higher level of mRNA expression TH, ChAT, GAP-43than both no SGstimulation and LSG stimulation(P＜0.05).6) Compared with SG stimulation, the AFinducibility was significantly decreased (P＜0.05), ERP was significantly prolonged (P＜0.05), dERP was significantly decreased (P＜0.05), and ERP rate-adaption wassignificantly recovered (P＜0.05) after stellate ganglionectomy both in RSG group andLSG group. Conclusion: Both RSG and LSG stimulation induced HR and SBP changes,low-level stimulation to RSG mainly induced HR changes, low-level stimulation to LSGmainly induced BP changes. RSG is mainly associated with RA AF, LSG is mainlyassociated with LA and PV AF. HRV can be increased, sympathetic and parasympatheticnerve activity can be enhanced by SG stimulation. The sympathetic activation occurredearlier and stronger than parasympathetic activation. There is good uniformity betweenHRV, neural discharge and plasma neurotransmitter level in evaluation of autonomicnerve activity. This uniformity highlight the importance of HRV as a good detectionmeans in evaluating the autonomic nerve activity in AF patients. Acute atrial electricalremodeling and acute autonomic neural remodeling may form a vicious cycle in whicheach perpetuates the other, thereby initiating and sustaining AF. This vicious cycle mayhelp to explain how AF maintains itself in its very early stage. The inhibition sympathetic nerve activation by unilateral stellate ganglionectomy can reverse atrial and PV electricalremodeling (reversal remodeling), which can reduce the AF initiating.