经胸心脏超声引导二尖瓣关闭不全大动物模型的建立

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目的:建立一种简便且稳定的二尖瓣关闭不全(MI)大动物模型,为后期开展的二尖瓣临床器械等的研发提供更好的参考。方法:选用20头雄性小尾寒羊(75~80 kg)建立MI模型,应用随机数字表法分为Sham组(n n=5)和MI组(n n=15)。采用经胸骨旁长轴超声切面引导下经颈动脉穿刺,用活检钳剪断二尖瓣腱索以建立MI模型,Sham组接受假手术,术后定期检查心功能等相关指标。术前大体资料采用非配对n t检验,超声数据采用配对样本n t检验。n 结果:实验组术后提示中量反流[(3.5±0.6) cmn 2],其中1头因心率失常死亡,2头死于急性左心衰,其余12头存活。而Sham组未见明显反流。术后3个月,MI组左室射血分数(LVEF)及左室短轴缩短率(LVFS)[(56.0±3.1)%、(32.2±2.6)%]均低于Sham组[(70.4±2.0)%、(38.1±3.3)%,n t=6.597、2.817,n P<0.05],此外,MI组左室舒张末容积(LVEDV)及左室收缩末容积(LVESV)[(83.5±1.7)、(28.4±1.5) ml]则高于Sham组[(74.5±1.8)、(21.4±1.6) ml,n t=6.057、3.603,n P<0.05]。同样,MI组左室舒张末直径(LVIDd)及LVIDs[(45.3±1.4)、(30.0±1.3) mm]也高于Sham组[(39.6±2.1)、(24.5±0.9) mm,n t=3.502、3.784,n P<0.05],心肌纤维化与心肌组织铁死亡GPX4增加而COX2降低。n 结论:此方法能够简便有效地建立MI模型,可用于MI的病理生理学研究,及经导管二尖瓣治疗产品的开发及评估。“,”Objective:To evaluate the physio-pathological features of mitral insufficiency (MI), and to establish a MI animal model of Ovis aries for the clinical instruments of mitral valve research.Methods:In this study, 20 male Ovis aries (75-80 kg) were randomly divided into MI group (n n=15) and Sham group (n n=5) by a random number table method. Animals underwent ultrasound-guided carotid puncture, and the mitral valve chord was cut with biopsy forceps to establish a MI model. The Ovis aries in the sham group followed the same procedure without cutting the mitral valve chord. The general characteristics of experimental animals were analyzed by unpaired n t-test, and the echocardiography results by paired n t-test.n Results:The area of color blood flow at mitral valve in the experimental group indicated moderate regurgitation [(3.5±0.6) cmn 2] post-operation. One of them died of arrhythmia, 2 died of acute heart failure 3 days after surgery, and the rest 12 survived. Three months later, the left ventricular ejection fraction [LVEF, (56.0±3.1)%] and left ventricular fraction shortening [LVFS, (32.2±2.6)%] in the experimental group were significantly lower than the sham group [(70.4±2.0)%, (38.1±3.3)%,n t=6.597, 2.817, n P<0.05]. The left ventricular end-diastolic volume (LVEDV) and the left ventricular end-systolic volume (LVESV) in the experimental group increased from [(74.5±1.8), (21.4±1.6) ml] to [(83.5±1.7) ml,n t=6.057, n P<0.05; (28.4±1.5) ml,n t=3.603, n P<0.05] compared to the sham group. The left ventricular internal diameter at end-diastole (LVIDd) and the LVIDs in the experimental group enlarged from [(39.6±2.1), (24.5±0.9) mm] to [(45.3±1.4) mm,n t=3.502, n P<0.05 and (30.0±1.3) mm,n t=3.784, n P<0.05] compared to the sham group. Meanwhile, GPX4 increased and COX2 decreased dramatically.n Conclusion:A safely and effectively mitral insufficiency animal model was successfully established, which could be used for the physio-pathological study of mitral insufficiency and the evaluation of clinical instruments of the mitral valve in preclinical studies.
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