Effects Of Trimetazidine On Atrial Electrical Remodeling And Atrial Muscle Cell Ultrastructure In Rapid Atrial Pacing In Rabbits

Objective: Atrial fibrillation,AF for short, is one of the most commoncardiac arrthythmia and the most common pathogenic factor for thrombusand heart failure in the elderly. The pathophysiology of AF is complex, themechanisms of AF are not completely understood at present. Recentevidence indicate that atrial electrical remodeling and structural remodelingis associated with the occurrence of atrial fibrillation. Recent study find thatpatients with atrial fibrillation in the changes of myocardial structure duringatrial fibrillation attack, which occurred in patients with atrial muscleremodeling.The purpose of this study was to investigate the effects ofantiarrthythmic drug trimetazidine on electrical remodeling by rapid atrialpacing on a rabbit model in the management area of AF and to propose anew way of prevention and treatment of AF.Methods: A total of20normal white rabbits were used in thisstudy,which are provided by hebei medical university animal experimentcenter. After measured body weight and heart rate, rabbits were randomlydivided into2groups: the saline group(control group, n=10), trimetazidinegroup (8mg/(kg.d), n=10).All rabbits were raised drugs in three weeks. Then,The electrode catheter was localized in right atrium through right internaljugular vein. Surface ECG and right atrial electrogram were recorded. Whenthe right atrial electrogram show amplitude of A ware significant more thanV wave, fixed the electrode catheter. The atrial effective refractory period(AERP) was measured by program stimulation at pacing cycle lengths of200ms and150ms respectively. Then, take a rapid atrial pacing (600bpm)and the AERP was measured after8hours pacing and30minutes after thetermination of rapid pacing. Electron microscopic studied the right auricular appendage tissue after the rapid pacing.SPSS13.0software packs were used for all the data to makestatistical-analysis. All values are expressed as mean±standard deviation.Continuous values were compared with repeated measurement dateMANOVA in same group. One-way ANOVA was used to evaluatedifferences between groups of discrete variables. We tookα=0.05as statisticsignificant level.Results:1The Time Course of Electrical RemodelingIn control group, the baseline AERP was112.61±9.0ms and103.55±4.8ms at BCL of200and150ms (Table1). After8hours rapidpacing AERP200and AERP150were97.30±6.8ms and93.24±5.0ms,whichsignificantly shortened15.32±3.5%(P<0.01) and10.31±1.5%(P<0.01).Because the degree of AERP shortening induced by rapid pacing was greaterat longer BCLs than that at shorter BCLs, physiological rate adaptation ofthe AERP was lost in the remodeled state.2Effects of trimetazidine on Electrical RemodelingIn the trimetazidine group, the AERP was not shortened during rapidpacing. The AERP at baseline113.91±9.6ms and103.33±4.7ms at BCLs of200and150ms) was not significantly different from the correspondingAERP after the termination of rapid pacing115.44±8.0ms and103.33±4.5msat BCLs of200and150ms, P>0.05)(Table1). physiological rate adaptationof the AERP was maintained in the remodeled state.3Stop pacing, impact on electrical remodeling after30minutesIn the control group, after the termination of rapid pacing, the AERPwere111.33±8.7ms and102.44±5.5ms at BCLs of200and150ms,In thetrimetazidine group, the AERP were111.33±8.7ms and102.44±5.5ms,nosignificant change in relative to the basic level(P>0.05)(Table1).4Atrial muscle cell ultrastructure changesElectron microscopic studies of right auricular appendage tissuedemonstrated that atrial muscle cells visible continuity of muscle damage, myofibril disappear, nuclear weeks height edema, mitochondria swelling,deformation, partly dissolved and disappeared, and rough endoplasmicreticulum expansion, highly visible scattered lipid droplets and spread inglycogen particles were observed in control group after8hours rapidpacing(Fig.1, Fig.2, Fig.3, Fig.4).Atrial muscle cells visible muscle fibers have good continuity,myofibril mild edema, part of the nuclear weeks mild edema, mitochondriaedema is lighter, did not see fat droplets and glycogen granules intrimetazidine group after the rapid atrial pacing,Trimetazidine significantlyreduced the changes of the ultrastructure of atrial muscle as a result of rapidpacing(Fig.7, Fig.8Fig.9, Fig.10, Fig.11, Fig.12).Conclusions:1Atrial rapid pacing can cause atrial electrical remodeling, whichdevelops quickly after pacing and recovers quickly after the termination ofrapid pacing.2Trimetazidine can prevent and reverse atrial electrical remodelingconduced by the rapid ventricular rate.3Trimetazidine can reduce changes of the ultrastructure of atrialmuscle cells conduced by rapid atrial pacing.