| Part One Electrical remodeling on atrium after 48 hours atrial tachy-pacing stop in Canine Models of Pacing-induced Atrial FibrillationObjective:To examine the reversibility of the changes in electrophysiological remodeling on atrium in dogs with paroxysmal atrial fibrillation.Methods:Twenty-six adult mongel dogs were randomly divided into 3 groups randomly,all of 26 dogs were anesthetized and intubated with a tracheal tube. 1. 48 hours pacing group(n=8):high-speed paced at a rate of 600 bpm.2. 24 hours reversing group(n=10): monitoring 24 hours after ATP stoped. Sham group(n=8): tracheal tube was implanted and there were no interventions. The parameters reflecting the change of atrial electrophysiology properties were observed , including ERP, CV, WL, adaptation of ERP, inducibility of atrial fibrillation. at 0 h,48 h, 52 h,60 h,66 h, 72 h. The current of L-type calcium channel of atrial muscle cell was recorded by patch clamp technique in the whole cell mode. Results:The ERP ,CV,WL, adaptation of ERP of the Sinus Rhythm group is less than those of the Sham group at 48 hour. After converted to sinus rhythm, the ERP, adaptation of ERP of Sinus Rhythm group recovered to the baseline.But CV,WL remained less than baseline. The density of ICa-L current was significantly decreased in 48 hours in atrail tachypacing group.After pacing stop 24 hours, The density of ICa-L current rebound to baseline level.Conclusion: Electrophysiological remodeling can be partially reversed 24 hours after AF converted to sinus rhythm. Part Two Reversion of Ibutilide on electrical remodeling of pulmonary vein during rapid Pacing induced atrial fibrillationObjective:To investigate the reversion effect of Ibutilide fumarate on electrical remodeling of atria in 48 hours atrial fibrillation canine model.Methods:Eighteen clinical healthy adult mongrel dogs were divided into 3 groups randomly:Pacing group (n=6) , Drug group (n=6) and sham group (n=6).For the Pacing group and Drug group: Pacing electrodes was implanted into high right atria through right femoral vein with high-speed Pacing at a rate of 600bpm for 48 hours. For the Sham group:Pacing electrodes was implanted but there were no interventions.Under the monitoring of electrocardiogram and hemodynamic, the Ibutilide fumarate were intravenously injected (0.001mg/kg/min), Ibutilide fumarate was repeatedly infused until cumulative dose was reached (0.04 mg/kg).The parameters reflecting the change of atrial electrophysiology properties were observed , including FD , fAPD,ERP,FA,WL,WOV.Results:When pacing stop, FD of Pacing and Drug group are faster than that of the Sham group),the ERP, fAPDof Pacing and Drug group are less than that of the Sham group.The ERP, adaptation of ERP of the Pacing and Drug group are less than that of the Sham group, after being administered with Ibutilide fumarate, all recovered to the baseline.The CV of the Pacing and Drug group are slower than that of the Sham group, after being administered with Ibutilide fumarate, it recovered to almost the baseline. The WOVof the Pacing and Drug group are wider than that of the Sham group, after being administered with Ibutilide, it reached to almost the baseline.The WOV of Pacing and Drug group are wider than that of the Sham group.After being administered with Ibutilide fumarate, all recovered to the baseline. Conclusion:Ibutilide fumarate has a positive effect on the retroconversion of pulmonary vein electrophysiological remodeling on prevention of paroxysmal atrial fibrillation. Part There Atorvastatin Restores Balances of Cardiac Nerve Function, Prevents Atrial Electrical Remodeling in a Canine Model of Atrial FibrillationObjectives:This study sought to systematically investigate flushing dose atorvastatin restores balances of cardiac nerve function, prevents atrial electrical remodeling in a canine model of atrial fibrillation Methods:18 dogs were randomly assigned into 3 groups:G1(n=6): G1 was a AF control group .Pacing electrodes was implanted into LAA with high-speed Pacing at a rate of 600bpm for 48 hours.G2(n=6): G2 was statin administration group. 7 days bofore operation,the dogs fed oral simvastatin (via feedstuff ) at a dose of 3 mg·kg-1,the other protocol are the same with G1. G3(n=6): G3 was a normal control group that underwent similar surgery and had been implanted pacing electrodes. Serial opened-chest electrophysiological studies were performed in each dog at baseline and 6, 12,18,24,30,36,42 and 48 hours after tachypacing onset. Immunocyto- chemical staining of cardiac nerves was performed using anti–GAP43, ChAT and TH antibodies.The mRNA expression of above factors were analysesed by semiquantitative RT-PCR. Results:The density of GAP43-positive, TH-positive and ChAT nerves in the RSPV were in GROUP2 were significantly lower than the nerve density in GROUP1 tissues,respectively. In constract ,the density of GAP43-positive, TH-positive and ChAT nerves in the RSPV, respectively, were equal to the nerve density in G2 tissues. Furthermore, in dogs with AF, the RA ,RSPV,RIPV had a significantly higher nerve density than other sites,this heterogeneity was not found in G2 and GROUP3. The changes of mRNA expression of GAP43,TH and ChAT in each GROUPs are coincidence with Immuno- cytochemical staining. Conversed with G1: ERP in G2 ,G3 was steady in the first 8 hours,and longer periods of rapid pacing(8 to 48 hours)failed to shorten the ERP at either 2×TH or 10×TH at each atrail and PVs site. Meanwhile,WOV and the ERP dispersion were unchanged throughout the 48-hour pacing period. In constract, ERP Dispersion In G1,the ERP dispersion was increased at the first 4 hour and then stabilized during the fourth to forty-eighth hour after pacing was started and WOV was progressively widened throughout the 48-hour pacing period.Conclusions:Flushing dose Atorvastatin prevents the electrophysiological and atrial fibrillation-promoting effects of atrial tachycardia-remodeling,possibly by anti never sprouting. |
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