【摘要】 目的研究迷走神经刺激(VS)诱发心房颤动(房颤)的情况及M2受体和IKACh在犬心房、心耳及其相邻大静脉的分布特点及胺碘酮对IKACh的影响,探讨其治疗胆碱能房颤的机制。方法10只犬分别给予切断迷走神经、VS、VS+胺碘酮(分别做为对照组、VS组和胺碘酮组)后,观察心房肌动作电位(APD)的变化及诱发房颤的情况。后分离出左右心耳、左右心房、肺静脉和上腔静脉,用Western印记法观察M2受体蛋白在上述组织的分布;并用组织块酶解法分离左右心耳、左右心房、肺静脉和上腔静脉的单个细胞,采用膜片钳全细胞法观察IKACh在上述部位的离子流密度;观察应用胺碘酮后IKACh的变化。结果对照组无一例诱发出房颤;VS组4例诱发房颤,诱发率为40％;胺碘酮组1例诱发房颤,诱发率为10％。胺碘酮组诱发房颤的比率比VS组有明显降低(P<0．05)。IKACh在左右心房都表现出强的内向整流性,在超极化有逐渐升高的内向电流,而在去极化表现快速衰减的外向电流,M2受体和IKACh电流密度显示在左右心耳和左心房比右心房、肺静脉和上腔静脉高[M2受体:0．66±0．08,0．67±0．08 and 0．51±0．06 vs 0．35±0．04,0．33±0．04 and 0．32±0．03,P<0．05;IKACh:(20．36±0．91)pA／PF,(21．34±0．92)pA／pF and(14．17±0．65)pA／pF vs(10．34±0．62)pA／pF,(8．24±0．45)pA／pF and (7．65±0．42)pA／pF,P<0．05];2 mM胺碘酮阻断后,IKACh密度明显降低,左右心房的IKAch密度没有明显差异,但心耳的密度仍比心房高。结论M2受体和IKACh电流密度在心耳明显高于心房和相邻静脉的分布,心耳可能在胆碱能房颤诱发中有重要作用,而肺静脉和上腔静脉的作用较小;胺碘酮可以阻断IKACh并减少左右心房IKACh大小的差异,此可能是其治疗胆碱能房颤的机制。更多还原

【Abstract】 Objective To investigate the effect of vagal stimulation ( VS) and amiodarone on atrial fibrillation(AF). Furthermore, To observe M2 receptor and acetylcholine-induced inward rectifier K+ current (IKACh)in supraventricular tissues and the effect of amiodarone on IKACh and cholinergic atrial fibrillation ( AF). Methods In 10 dogs, action potential duration(APD) and AF were determined at 24 sites during bilateral cervical vagal trunks cut (control group) , VS ( VS group) , VS plus amiodarone administration ( amiodarone group). After electrophysiological measurement, the hearts were quickly excised. Then right atrial appendage (RAA) , left atrial appendage (LAA) , right atrium (RA) , left atrium (LA) , pulmonary veins (PV) and superior vena cava (SVC) were dissected. Western-blot and patch clamp were used to determine M2 receptor and IKACh.The effect of amiodarone on IK,Ach were observed. Results AF was induced in four dogs in VS group, and in one dog in amiodarone group, but not be induced in control group. The induced ratio of AF in amiodarone group is lower than that in VS group. IKACh demonstrated strong inward rectification with increasing inward currents during hyperpolarizing voltage steps and rapidly decaying outward currents during depolarization. The densities of M2 receptor and IKACh in LAA, RAA and LA were higher than that in RA, PV and SVC[ M2 receptor; 0. 66±0.08,0. 67±0.08 and 0.51±0. 06 vs 0. 35±0. 04, 0.33±0.04 and 0.32±0.03 P <0. 05;IKACh: (20. 36±0.91) pA/pF, (21.34±0.92) pA/pF and (14. 17±0.65) pA/pF vs (10.34±0.62) pA/pF, (8. 24±0. 45) pA/pF and (7. 65±0. 42) pA/pF, P<0. 05]. Furthermore, the densities of the M2 receptor and IKACh in LAA and RAA were higher than that in LA(P<0. 05). After amiodarone administration, densities of IKACh in LA and RA had no difference, but densities of IKACh were also less in atrium than in atrial appendage. Conclusions Densities of the M2 receptor and IKACh are higher in atrial appendage than other sites. Atrial appendage perhaps plays an important role in initiation of cholinergic AF. Reduced dispersion of IKACh is the mechanism for amiodarone to cure AF.更多还原