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Objective In this research we established rapid atrial pacing rabbit models, to investigate the effects of simvastatin on changes of early atrial effective refractory period (AERP) and protein expression of atrial α1c sub-unit of L-type calcium channel on atrial remodeling. Methods 42 rabbits were randomly divided into 3 groups:control group,rapid pacing group and simvastatin group,simvastatin 5 mg/( kg·d) was given intragastrically daily for two weeks before electrophysiology study in simvastatin group, normal saline was given intragastrically in control and rapid pacing group instead. Control group with no pacing, in simvastatin group and rapid pacing group, right atrium was paced at 800 beats/min for 8 hours to establish acute atrial fibrillation models, right atrial effective re-fractory period(AERP)was measured at the basic cycle length of 200 ms and 150 ms before pacing and 1,2,4,6, and 8 hours after the onset of the pacing, the changes of rate adaptation of AERP (AERP200-AERP150) were ana-lyzed . Right atrium tissue was obtained for measurement of protein expression of atrialα1 c subunit of L-type calcium channel by Western blot. Simultaneously,lipid levels in each group was examined. Results No significant differ-ence in lipid levels among three groups was observed. The AERP was shortened and the rate adaptation of AERP (AERP200-AERP150) disappeared during pacing compared with those before pacing(P<0.05). The shortening of AERP was reversed and AERP200-AERP150 was maintained in simvastatin group. Compared with the control group,the protein expression levels of atrial α1c subunit of L-type calcium channel decreased significantly after 8 hours pacing in rapid pacing group(P<0.01). The protein expression levels of simvastatin group decreased insig-nificantly . Conclusion Atrial rapid pacing can induce the shortening of the AERP and the losing of adaptability to the frequency of AERP,pretreatment with simvastatin can improve the degree significantly and maintain the adapta-bility to frequence basically. The protein expression levels of atrial α1c subunit of L-type calcium channel de-creased significantly after 8 hours pacing,pretreatment with simvastatin can prevent this change without lowering the lipid levels,thus contributing to the ionic mechanism of simvastatin for antiarrhythmia.
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Objective To investigate the impact and significance of the vagus nerve intervention on the atrial electrical emodeling.Methods 30 mongrel dogs were given metoprolol in order to eliminate the effects of sympathetic nerve on atrial electrical remodeling;observe the atrial effective refractory period (ERP) and atrial fibrillation susceptible window(VW) in the high right atrial(SA) and coronary sinus (CS) by the vagus nerve stimulation(VS) or vagus nerve stimulation(Non-VS) before and after using atropine and after atrial electrical remodeling was observed.Results Before using vagus nerve blocking agents atropine,ERP shortened significantly [(54.83 ± 46.23) ms] and VW increased significantly [(19.86±13.23) ms] after VS,this time with atrial fibrillation-prone ; After using atropine,ERP increased significantly [(112.33 ± 9.63) ms] under VS,did not induce atrial fibrillation; After atrial electrical remodeling,the value of ERP was no significant difference under basis and VS (t =2.116,0.853,all P ＞0.05).Conclusion VS can increase the atrial electrical remodeling,an increase of atrial fibrillation susceptibility;vagus nerve block can reduce atrial electrical remodeling and atrial fibrillation susceptibility decreased.
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Background Atrial electrical remodeling(AER)plays an important role in the pathogenesis and maintenance of atrialfibrillation.However,little is known about modulation of vagal activilty to AER.This study aimed to investigate the relationshipbetween vagal moduation and AER. Methods Twenty four adult mongrel dogs under general anesthesia were randomized into 3groups.Sympathetic activity was blocked by administration of metoprolol in 3 groups.The changes in vagal modulation to atria afterAER were observed in 10 dogs without vagal interruption in group A.The effects of vagal intervention on AER were investigated in 8dogs with administration of atropine in group B.The impact of aggressively vagal activity on AER was studied in 6 dogs with bilateralcervical vag sympathetic trunLks stimulation during AER in group C.Bilateral cervicall vagosympathetic trunks were decentralized.Multipolar catheters wereplaced into high right atria(RA),coronary sinus(CS)and rightventricle(RV).AER was induced by 600 bpmpacing through RA catheter for 30 minutes.Attial effective refractory period(ERP)and vulnerability window (VW)of atrial fibrillationwere measured with and without vagal stimulation before and after AER.Results In group A,ERP decreased significantly at baselineand during vagal stimulation after AER compared with that beforeAER(all P＜0.05).In group B,ERP remaind unchanged at baselineand vagal stimulation after AER compared with tbat before AER (all P＞0.05).In group C,ERP shortened significantly at baseline andvagal stimulation after AER compared with that before AER(all P＜0.05).ERP shortening after AER in Groups A and C increasedsignificantly than that in group B (all P＜0.05).Atrial fibrillation could not be induced at baseline(VW close to 0) before and after AERin three groups.VW became widen significantly during vagal stimulation after AER compared with that before AER in Groups A and C(all P＜0.05),while VW remained unchanged in group B (VW close to 0).Conclusions Short-term AER results in the decrease inERP.AER is accompanied by the increases in atrial vagal modulation.The increased vagal activity and vagal stimulation promote AER,thereby increase the susceptibility to atrial fibrillation.The interrupted vagal activity attenuates AER.thereby suppresses the atriaIfibrillation mediated by vagal stimutlation.
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Objective To inquire into T-type calcium channel effects on atrial electrical remodelling and its mechanisms during atrial fibrillation.Methods Animal experiment was performed in Peking University Pepole's Hospital from Feb.2002 to Oct.2006.Fifteen adult cross-bred dogs were used in the experiment.Ten dogs underwent continuous rapid atrial pacing(500 beats/min)for twenty-four weeks to create persistent atrial fibrillation.In five rapidly-paced dogs,50mg pure powder/day of mibefradil dihydrochloride was given from the second day after pacemaker implantation and continued until the twenty-fourth week.A group of size-matched dogs(n=5)without being given mibefradil was used as a pure atrial fibrillation group.Another group of size-matched dogs(n=5)without pacemaker implantation was used as a control group.Atrial fibrillation duration was determined by electrophysiological study.Canine atrial myocytes were isolated by enzymatic dissociation and intracellular Ca2+ cytosolic transient was studied with confocal imaging.Results (1)The preoperation atrial effective refractory period was 280/90~110 ms.In the twenty-fourth week after rapid atrial pacing,atrial effective refractory period was obviously extended(2000/1400~1700 ms)in the T-type Ca2+ channel blocker group compared with the preoperation one.In the twenty-fourth week,the induced rate of persistent atrial fibrillation was 75% in atrial fibrillation group,whereas the persistent atrial fibrillation occurred in only one case(20%)in the T-type Ca2+ channel blocker group.(2)Intracellular Ca2+ concentration of atrial myocytes was unremarkably changed in control group after blocking L-type Ca2+ channel(1.17?0.09 OD ratio),whereas the intracellular Ca2+ concentration was obviously enhanced(2.35?1.05 OD ratio)(P
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BACKGROUND: Pacing-induced atrial electrical remodeling (AER) is characterized by shortening of atrial effective refractory period (A-ERP) and its altered rate adaptation. In paroxysmal atrial fibrillation (AF), periods of AF occur with interveneing normal sinus rhythm (NSR) when atria recover from the preceding AER. Previous episodes of AF may precondition the atrial myocardium and cause different time course of AER in subsequent episodes of AF. But the influence of the preceding AER on the subsequent AER has not been described. METHODS: Four mongrel dogs were anesthetized with enflurane. After thoracotomy, silicon band with 3 pairs of electrodes was sutured to the lateral wall of the left atrium. Atrial pacing was performed after 2 wks of recovery and autonomic blockade. Pacing protocol consisted of rapid atrial pacing (RAP) at 500 bpm (for 60 min) and recovery in NSR (for 60 min) which was repeated three times. A-ERP was measured every 10 min. The same pacing protocol was repeated after pretreatment with verapamil (0.1 mg/kg/hr). RESULTS: 1) With 60 min of RAP, A-ERP decreased significantly (126+/-6 ms vs. 105+/-7 ms, p<0.005). 2) After cessation of pacing, A-ERP returned to 98% of baseline value in 15 minutes. Recovery from AER occurred faster than AER (78 vs 21 ms/h). 3) After pretreatment with verapamil, RAP decreased A-ERP from 127+/-5 ms to 116+/-5 ms. AER, the reduction in A-ERP, was significantly attenuated by pretreatment with verapamil (deltaERp=17+/-7 vs. 9+/-0.2 %, p<0.05). 4) When RAPs were repeated, AER showed a tendency of acceleration, but it was not statistically significant (deltaERp=22 ms, 24 ms, 28 ms at the end of 60 min pacing for the 1st, 2nd, 3rd pacing). CONCLUSION: RAP induced AER in conscious dog atria and it was reduced by pretreatment with calcium channel blocking agent, verapamil. Upon repeated atrial stimulations, AER did not accelerate or decelerate when the atria recovered from the preceding AER.