妊娠中晚期胎羊宫内心脏介入治疗实验

Intra-utero fetal cardiac intervention in medium and late pregnancy stages in the fetal lamb

背景:严重心血管畸形的胎儿出生后预后极差,孕中、后期干预可以明显改善患胎预后,通过动物实验对妊娠中晚期宫内心脏进行介入,可建立安全、有效、可行的实验动物模型。目的:以妊娠中晚期孕羊为实验对象,探讨宫内心脏模拟介入治疗的可行性。设计、时间及地点:随机分组,对照观察,于2007-09/2008-02在四川大学华西科技园移植病理技术平台及麻醉技能实验室完成。材料:选用9只双胎妊娠101～127d(term150d)黑山羊。方法:随机将每只黑山羊双胎之一做为心脏介入治疗组,另一只设为对照组,每组9只。治疗组麻醉后穿刺胎羊心前区胸壁后进入左心室,进行胎羊宫内心脏介入治疗。对照组胎羊同时暴露在麻醉、介入治疗过程中,但不对其进行介入操作。主要观察指标:①腹部超声监测胎羊心率变化情况。②胎羊血气、血糖及血乳酸值。③苏木素-伊红染色,肝组织PAS染色观察胎羊/新生羊的脑、肝、肺组织形态。结果:介入治疗组胎羊出现血pH降低及心脏穿刺时一过性心率下降、早搏二联律,介入治疗后胎羊血糖及血乳酸较术前升高(P<0.05),新生羊期血pH、血糖及血乳酸均恢复正常,实验过程中胎羊血电解质保持稳定。3/9孕羊被处死,3/9只妊娠羊经阴道早产,3/9只妊娠羊经阴道足月分娩,新生羊存活,胸壁皮肤未见瘢痕形成。脑组织病理学检查:1例介入治疗组新生羊有轻度病理学变化,其余介入治疗组新生羊/胎羊与对照组新生羊/胎羊脑组织结构均无异常;肺组织病理学检查均未见有明显病理学改变;肝组织PAS染色显示心脏介入治疗后肝糖原大量消耗,继续妊娠后肝糖原蓄积恢复。结论:实验构建了先天性心血管畸形胎儿宫内介入治疗的动物实验模型,表明利用妊娠中晚期孕羊进行胎羊宫内心脏介入治疗是可行的。

BACKGROUND： Prognosis of new-born fetuses with serious vascular malformation is very poor. An animal experiment was performed to establish a safe, effective and feasible animal model undergoing treatment with the intra-utero fetal cardiac intervention which can obvious improve the fetal prognosis. OBJECTIVE： To evaluate the feasibility of intra-utero fetal cardiac intervention in medium and late pregnancy stages in the goat fetuses. DESIGN, TIME AND SETTING： The randomized control grouping observation was performed at the Transplantation Technology Platform of West China Science and Technology Park, Sichuan University, from September 2007 to February 2008. MATERIALS： Nine bigeminal pregnant black goats with a pregnancy period of 101-127 days were enrolled. METHODS： One fetus from each pregnant goat was taken as the intervention group, and the other one as control group. Intra-utero cardiac intervention therapy was underwent through puncture needle insertion into the left ventricle via the precordium chest wall after anesthesia. There was no intervention treatment in the control group. MAIN OUTCOME MEASURES： Changes in heart rate, blood gas, blood glucose, and blood lactate of fetal lambs were observed. Fetal hepatic PAS staining, and HE straining were used to evaluate histopathological changes of brain, lung and liver in fetal and newborn lambs. RESULTS： While cardiocentesis, pH value reduce, transient decrease of heart rate and bigeminal premature contractions occurred in the intervention group. Blood glucose and blood lactate increased following cardiac intervention （P 〈 0.05）. pH value, blood glucose and blood lactate levels recovered to the normal in the newborn goats. During procedures, fetal electrolyte kept stabilization. Of the 9 goats, 3 goats were executed after intervention, 3 goats came to full-term delivery and 3 goats to premature delivery. The living newborn goats had no inflammation and scar formation on the chest wall. Histological examination of brains and lungs from the fetal lambs and newborn goats demonstrated that there were no differences between the two groups except that only one fetal lamb in the intervention group showed mild pathologic changes in the brain tissue. PAS staining for liver tissues showed a great consumption of hepatic glycogen during fetal cardiac intervention, which could be re-accumulated in the following gestation. CONCLUSION： Intra-utero fetal cardiac intervention in near-term fetal lambs is feasible using an animal model of congenital cardiovascular malformation.