Influence Of Cyclosporine A On Atrial Fibrillaton Of Canine

Background and ObjectiveAtrial electrical remodeling(AER) induced by atrial fibrillation(AF) plays an important role in the development of AF.The mechanism of AF-induced AER is due to the alteration of atrial electrophysiological property and underlying ion channels provoked by AF.During the alteration,the key point is the activation of calcinerin signaling pathway.The purpose of this study is to evaluate the influence of cyclosporine(CsA),an inhibitor of calcineurin signaling pathway,on the atrial electrophysiological property and the expression of ion channel proteins in a canine model of AF.MethodsEighteen healthy male mongrel dogs(weight 17.0～23.2kg,aged 2.0～ 4.0 years) were divided into three groups:AF, sham and CsA group.1.0n the establishing of canine AF model,multielectrode catheters were positioned at the lateral right atrium and right ventricle apex transvenously for local electrical stimulation and electrogram recording.The parameters including P wave duration,atrial efective refractory period(AERP),the adaption of AERP to rate,conduction velocity(CV) and wave length(WL) were measured,compared and analyzed between different groups.2.After 8 weeks pacing,thoracotomy was performed and samples of cardiac tissue were obtained.Western Blot was used to examine the expression of ion channel proteins of the atrial myocyte.Results1 .Atrial electrophysiological propertiesCompared to sham group, AF and CsA groups had a longer duration of the P wave (P<0.05),shorter AERP (P<0.05),decreased adaptation of AERP(P<0.01),slower CV (P<0.01) and shorter WL (P<0.01).In comparison to AF group,CsA group had a longer AERP(P<0.05) and a recovering tendency of other parameters but without statistical significance.2.Expression of atrial ion channel proteinsCompared to sham group,AF and CsA groups had reduced proteins expression,including L-type Ca²⁺ channel α 1c subunit, K⁺ channel Kv1.5 and Kv4.3(P<0.01,for all).Compared to AF group,CsA group had increased expression of the above proteins(P<0.01,for all).ConclusionsThe reversion of pacing-induced alteration of atrial ion channel proteins expression induced by CsA can not lead to the reversion of atrial electrophysiological properties.Therefore, we postulated that AER is a complex process in which many different processes influence and modulate each other. Single or fewer signaling pathway interference could not effectively control the initiation and maintenance of AF.