| Atrial fibrillation,one of the most common arrhythmia in clinic practice,is associated with high morbidity,serious complications and complex pathogenesis,while the application of traditional anti-cardiac arrhythmia drugs is limited due to its cardiac arrhythmia and related side effects.Although the pathophysiology of atrial fibrillation is not yet fully understood,it has been showed in the domestic and international studies that atrial fibrillation may cause atrial electrical physiological changes,which can promote the occurrence and maintenance of atrial fibrillation,called atrial electrical physiological remodeling(short for electrical remodeling).Along with the research,some non-traditional anti arrhythmia drugs,aimed at the pathogenesis,are brought into the field of atrial fibrillation prevention and control.The non lipid lowering effect of statins has been paid more and more attention,and atrovastatin has the most experimental evidences,while the effect of atovastatin on atrial remodeling induced by atrial fibrillation and potential mechanism has not yet totally clear.Objective: We established the animal models of rabbits with atrial fibrillation by the method of epicardium electrode implantation and animal cardiac pacemaker rapidly pacing,pretreatment with atorvastatin or placebo.Examining the atrial effective refractory period and rate adaptability of electrophysiological changes,detecting the ion channel protein expression and cardiac structure and function,to investigate the effect of atovastatin on atrial remodeling induced by atrial fibrillation and potential mechanism.Methods: We selected thirty New Zealand white rabbits as experiment subjects,whose wright vary from 2.5kg to 3.0kg,provided by the Test Animal Center of Hebei Medical University.Thirty rabbits were randomly divided into three groups:control group(NP),pacing group(ATP)and medicine group(ATO),and subjected to atrial tachypacing as atrial fibrillation models at 600 bpm.The tachypacing model were performed by attaching pacing and testing electrodes to left atrial and connecting with custom animal cardiac pacemaker in open-chest situation.The medicine group were pretreated with atorvastatin in dose of 2mg/(kg·d)for seven days,and accept tachypcing for 48 hours together with the pacing group,continuing with medicine therapy and monitoring electrocardiogram for uncontinued pacing.Serial atrial effective refractory period(AERP)were measured in each rabbit at baseline and 8,16,24,32,40,and 48 hours with different cycle lengths.The changes of cardiac functions and cardiac structure were observed by cardiac ultrasonic cardiogram before and after atrial tachypacing.The expression of atrial ion channel proteins CaL?1 and Kv4.3 were detected by Western-Blot method.Results:1 The result of experimental animals: We established the rabbit atrial fibrillation models by the method of epicardium electrodes implantation and animal cardiac pacemaker rapidly pacing.There were twenty-eight rabbits survived after the operation,and twenty-four were integrally collected after tachypacing.Two of the animals died of atrial rupture due to electrodes in control group.There were two animals eliminated for deficient data in pacing and medicine group,respectively.Finally,we made only twenty-four successful models:eight animals in each group.2 Changes of atrial effective refractory period AERPThere was no significant difference for basic between the three groups at different pacing cycles.After tacypacing for eight hours,AERP at cycle of 150ms(short for AERP150)pacing group was shortened by 6.49 ms and compared with control group,by 7.74ms(P<0.05).Along with pacing,AERP150 continued shortening,up to 20% after 48 hours' tachypacing.While,the degree of change of AERP150 in medicine group was less,totally shortened by 15.0ms and 15.15%,and the difference was statistically significant,compared with control group(P<0.05).Similarly,the AERP200 of pacing and medicine groups were shorter than control group after 48 hours' pacing,especially the pacing group,there were statistically different between three groups.3 Changes of the adaption of AERPThe general status of adaption of AERP was similar between groups before atrial tachypacing(P>0.05),while the pacing group showed the most obvious change and,seriously decreased followed by pacing course(P<0.05),in contrast,the change was limited in the medicine group apparently(P>0.05).4 Changes of the cardiac structure and functionThe basic status of animals before pacing: There were no statistical differences among three groups in measurement of cardiac ultrasound,such as LAD?LVESD?LVEDD?LVEF(P>0.05).After pacing for 48 hours,LAD in pacing and medicine groups were decreased(P<0.05),but there is no difference between the two groups(P>0.05).While LVEDD?LVSED?LVEF were similar among groups before and after pacing(P>0.05).5 Changes of expression of atrial ion channel proteins CaL?1 and Kv4.3Compared with control group,the level of atrial ion channel proteins CaL?1 and Kv4.3 expression markedly decreased(P<0.05),however,the effect was attenuated in medicine group(P<0.05).The positions of bands of the target proteins and ?-actin protein were matched with theory of gray value.Conclusion:1 Atrial electrical remodeling of rabbits can be induced by atrial tachypacing.2 Atorvastatin pretreatment can significantly attenuate the atrial acute electrical remodeling in rabbits induced by atrial tachypacing,an effect not shared by cardiac structure.3 The potential mechanism may be the inhibition of down-regulation of atrial ion channel proteins CaL?1 and Kv4.3 expression. |
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