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
张玲,孟庆军,贾索尔·肖克热提,李杨,王雪生,周贤惠,汤宝鹏
摘要(Abstract):
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。
关键词(KeyWords): 慢性阻塞性睡眠呼吸暂停综合征模型;心房颤动(AF);犬;电镜
基金项目(Foundation): 国家自然科学基金(81560064,81670292,81560063)
作者(Author): 张玲,孟庆军,贾索尔·肖克热提,李杨,王雪生,周贤惠,汤宝鹏
参考文献(References):
- [1]GOUDIS C A,KETIKOGLOU D G.Obstructive sleep and atrial fibrillation:Pathophysiological mechanisms and therapeutic implications[J].Int J Cardiol,2017,230:293-300.
- [2]PUNJABI N M,CAFFO B S,GOODWIN J L,et al.Sleepdisordered breathing and mortality:aprospective cohort study[J].PLoS Med,2009,6(8):e1000132.
- [3]MARIN J M,AGUSTI A,VILLAR I,et al.Association between treated and untreated obstructive sleep apnea and risk of hypertension[J].JAMA,2012,307(20):2169-2176.
- [4]MANSUKHANI M P,CALVIN A D,KOLLA B P,et al.The association between atrial fibrillation and stroke in patients with obstructive sleep apnea:apopulation-based case-control study[J].Sleep Med,2013,14(3):243-246.
- [5]PEDROSA R P,DRAGER L F,GENTA P R,et al.Obstructive sleep apnea is common and independently associated with atrial fibrillation in patients with hypertrophic cardiomyopathy[J].Chest,2010,137(5):1078-1084.
- [6]NARUSE Y,TADA H,SATOH M,et al.Concomitant obstructive sleep apnea increases the recurrence of atrial fibrillation following radiofrequency catheter ablation of atrial fibrillation:clinical impact of continuous positive airway pressure therapy[J].Heart Rhythm,2013,10(3):331-337.
- [7]SHUKLA A,AIZER A,HOLMES D,et al.Effect of obstructive sleep apnea treatment on atrial fibrillation recurrence:A meta-analysis[J].JACC Clin Electrophysiol,2015,1(1/2):41-51.
- [8]VALENZA M C,BARANCHUK A,VALENZA-DEMET G,et al.Prevalence of risk factors for atrial fibrillation and stroke among 1210patients with sleep disordered breathing[J].Int J Cardiol,2014,174(1):73-76.
- [9]BRAGA B,POYARES D,CINTRA F,et al.Sleep-disordered breathing and chronic atrial fibrillation[J].Sleep Med,2009,10(2):212-216.
- [10]HOLMQVIST F,GUAN N,ZHU Z,et al.Impact of obstructive sleep apnea and continuous positive airway pressuretherapy on outcomes in patients with atrial fibrillation-results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation(ORBIT-AF)[J].Am Heart J,2015,169(5):647-654.
- [11]BASNER R C.Cardiovascular morbidity and obstructive sleep apnea[J].N Engl J Med,2014,370(24):2339-2341.
- [12]GAO M,ZHANG L,SCHERLAG B J,et al.Low-level vagosympathetic trunk stimulation inhibits atrial fibrillation in a rabbit model of obstructive sleep apnea[J].Heart Rhythm,2015,12(4):818-824.
- [13]GHIAS M,SCHERLAG B J,LU Z B,et al.The role of ganglionated plexi in apnea-related atrial fibrillation[J].J Am Coll Cardiol,2009,54(22):2075-2083.
- [14]ZHAO J,XU W,YUN F,et al.Chronic obstructive sleep apnea causes atrial remodeling in canines:mechanisms and implications[J].Basic Res Cardiol,2014,109(5):427.
- [15]GOTTLIEB D J.Sleep apnea and the risk of atrial fibrillation recurrence:Structural or functional effects[J]?J Am Heart Assoc,2014,3(1):e000654.
- [16]ZHANG L,HOU Y M,PO S.Obstructive sleep apnea and atrial fibrillation[J].Arrhythm Electrophysiol Rev,2015,4(1):16-18.
- [17]张玲,郭玉君,孙娟,等.迷走神经刺激建立迷走神经介导的急性房颤犬模型[J].新疆医科大学学报,2012,35(12):1595-1599.
- [18]CORTESE R,GILELES-HILLEL A,KHALYFA A.Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea:Potential role of CD36[J].Sci Rep,2017,(7):43648.
- [19]吴晓丹,黄建浩,孔德红,等.慢性间歇低氧大鼠模型的建立和超声心动图评价[J].复旦学报(医学版),2011,38(6):481-517.
- [20]王伊宁,李森恺,叶京英,等.应用肉毒杆菌毒素建立阻塞性睡眠呼吸暂停低通气综合征动物模型的研究[J].中国耳鼻咽喉头颈外科,2010,17(9):485-487.
- [21]聂莉,鲁志兵,何勃,等.睡眠呼吸暂停低通气综合征并发心房颤动的实验模型[J].中国心脏起搏与心电生理杂志,2013,27(1):40-43.
- [22]YU L,HUANG B,WANG Z,et al.Impacts of renal sympathetic activation on atrial fibrillation:The potential role of the autonomic cross talk between kidney and heart[J].J Am Heart Assoc,2017,6:e004716.