慢性犬阻塞性睡眠呼吸暂停并发心房颤动模型的构建及对心房电生理和超微结构的影响  

Establishment of atrial fibrillation associated with chronic obstructive sleep apnea syndrome model and its effect on atrial electrophysiology and structural remodeling

作　　者：张玲[1] 孟庆军[1] 贾索尔.肖克热提 李杨[1] 王雪生 周贤惠[1] 汤宝鹏[1] ZHANG Ling;MENG Qinjun;Jiasuoer Xiaokereti;LI Yang;WANG Xuesheng;ZHOU Xianhui;TANG Baopeng(Department of Cardiac Pacing and Electrophysiology,the First Affloated Hospital,Xinjiang Medical University,Urumqi 830054,Xinjiang,China)

机构地区：[1]新疆医科大学第一附属医院心脏起搏与心电生理科,乌鲁木齐830054

出　　处：《新疆医科大学学报》2018年第6期731-736,共6页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(81560064;81670292;81560063)

摘　　要：目的构建犬慢性阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome,OSA)并发心房颤动(atrial fibrillation,AF)的动物实验模型,观察慢性OSA对犬心房电生理特性及组织结构的影响。方法在麻醉下气管插管的6只比格犬行人为的反复气道阻塞,每天4h,共持续3个月,建立慢性呼吸暂停模型。通过程序刺激(S1S2)诱导AF模型,观察造模前、造模后第1、2、3个月气管插管堵塞前、后pH值、二氧化碳分压(PCO_2)、氧分压(PO_2)及观察造模前、造模后第1、2、3个月右心房有效不应期(effective refractory period,ERP)和AF持续时间。通过HE及电镜观察右心房大体及超微结构的变化。6只比格犬麻醉气管插管,但不堵塞气管插管,作为对照取组织进行HE及电镜。结果所有犬均造模稳定,动物状态良好,与干预前相比较,3个月后PO_2和pH值逐月降低,PCO_2逐月增加,提示造模成功。犬心房ERP逐渐缩短和AF持续时间逐渐延长(P<0.05)。心房肌组织结构明显紊乱,部分心肌纤维断裂、溶解,坏死部位肌间质线粒体聚集,线粒体大小、形态不一,部分线粒体肿胀,脊膜结构不清晰,部分线粒体萎缩、体积缩小。结论本方法能够成功构建稳定、可重复性好的犬慢性睡眠呼吸暂停并发心房颤动的动物模型,犬心房ERP逐渐缩短和AF持续时间逐渐延长,心房肌结构明显紊乱。本AF模型可应用于慢性OSA病理生理机制及相关研究。Objective To establish chronic atrial fibrillation（AF）model associated with obstructive sleep apnea syndrome（OSA）on canine.Atrial electrophysiology characteristic and structural remodeling was observed on canine model.Methods Chronic OSA model was established on six anaesthetized beagle canine with endotracheal tube by repeatedly stopping the ventilator for 4 hper day and lasting for 12 weeks.Atrial effective refractory period（ERP）and atrial fibrillation duration were measured by programmed stimulation（S1S2）,blood pressure and blood gases（O2,CO2,pH）were determined before and after episode of OSA at baseline,the end of the first month,second month and third month.Atrial ERP and AF duration also were determined.After 3 months,HE stain and electron microscope were performed on right atrium tissue.Six canine with sham endotracheal occlusion as control group.Results In chronic canine model,repeated apnea lead to a substantial decrease in the arterial PO2 and pH level and an increase in the PCO2 level.ERP began to lengthen progressively,AF duration increased progressively.In chronic OSA model,arterial PO2,pH value decreased and increased in the PCO2 with month increase（P〈0.05）.ERP lengthen and AF duration increased progressively from the 1 st month.Some of the atrial myocardial fibers were broken and dissolved,and the mitochondria in the necrotic area were aggregated.The size and shape of mitochondria were different.Most atrial in the OSA group exhibited an obvious disorder of the tissue structure,some mitochondria swelled,and the spinal membrane structure was not clear,some mitochondria atrophied and the volume was reduced.Conclusion This method can provide chronic steady and repeatable AF associated with obstructive sleep apnea syndrome model on canine.The model can be applied to the investigation of pathogenesis and pathophysiology of OSA.

关 键 词：慢性阻塞性睡眠呼吸暂停综合征模型 心房颤动(AF) 犬 电镜 

分 类 号：R541.7[医药卫生—心血管疾病]