Hodges Ryan, Endo Masayuki, La Gerche Andre, Eixarch Elisenda, DeKoninck Philip, Ferferieva Vessilina, D'hooge Jan, Wallace Euan M, Deprest Jan
Division Woman and Child, Department Women, University Hospitals Leuven.
J Vis Exp. 2013 Jun 29(76):50392. doi: 10.3791/50392.
Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ultrasound and fetal echocardiography. Increasingly, these imaging modalities are being employed clinically to examine cardiac function and assess wellbeing in utero, thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR that allows analysis of cardiac function in a clinically relevant way. Using isoflurane induced anesthesia, IUGR is surgically created at gestational age day 25 by performing a laparotomy, exposing the bicornuate uterus and then ligating 40-50% of uteroplacental vessels supplying each gestational sac in a single uterine horn. The other horn in the rabbit bicornuate uterus serves as internal control fetuses. Then, after recovery at gestational age day 30 (full term), the same rabbit undergoes examination of fetal cardiac function. Anesthesia is induced with ketamine and xylazine intramuscularly, then maintained by a continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic effects on fetal cardiac function. A repeat laparotomy is performed to expose each gestational sac and a microultrasound examination (VisualSonics VEVO 2100) of fetal cardiac function is performed. Placental insufficiency is evident by a raised pulsatility index or an absent or reversed end diastolic flow of the umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery Doppler is then examined. Fetal echocardiography is performed by recording B mode, M mode and flow velocity waveforms in lateral and apical views. Offline calculations determine standard M-mode cardiac variables, tricuspid and mitral annular plane systolic excursion, speckle tracking and strain analysis, modified myocardial performance index and vascular flow velocity waveforms of interest. This small animal model of IUGR therefore affords examination of in utero cardiac function that is consistent with current clinical practice and is therefore useful in a translational research setting.
胎儿宫内生长受限（IUGR）会导致心脏功能异常，由于胎儿胎盘多普勒超声和胎儿超声心动图技术的进步，这种异常在产前就很明显。越来越多的，这些成像方式被临床用于检查心脏功能并评估子宫内的健康状况，从而指导出生决策的时机。在此，我们使用了一种IUGR兔模型，该模型能够以临床相关的方式分析心脏功能。采用异氟烷诱导麻醉，在妊娠第25天通过剖腹手术创建IUGR，暴露双角子宫，然后结扎单个子宫角中为每个妊娠囊供血的40 - 50%的子宫胎盘血管。兔双角子宫的另一个角作为内部对照胎儿。然后，在妊娠第30天（足月）恢复后，对同一只兔子进行胎儿心脏功能检查。通过肌肉注射氯胺酮和赛拉嗪诱导麻醉，然后通过持续静脉输注氯胺酮和赛拉嗪维持麻醉，以尽量减少对胎儿心脏功能的医源性影响。再次进行剖腹手术以暴露每个妊娠囊，并对胎儿心脏功能进行微型超声检查（VisualSonics VEVO 2100）。脐动脉多普勒波形的搏动指数升高或舒张末期血流缺失或反向表明胎盘功能不全。然后检查静脉导管和大脑中动脉多普勒。通过记录侧视图和心尖视图中的B模式、M模式和流速波形进行胎儿超声心动图检查。离线计算确定标准M模式心脏变量、三尖瓣和二尖瓣环平面收缩期偏移、斑点追踪和应变分析、改良心肌性能指数以及感兴趣的血管流速波形。因此，这种IUGR小动物模型能够对子宫内心脏功能进行检查，这与当前临床实践一致，因此在转化研究环境中很有用。
