Teillet Baptiste, Manœuvrier Florian, Rougraff Céline, Besengez Capucine, Bernard Laure, Wojtanowski Anne, Ghesquieres Louise, Storme Laurent, Mur Sébastien, Sharma Dyuti, Le Duc Kévin
Department of Neonatology, Pôle Femme-Mère-Nouveau-Né, Hôpital Jeanne de Flandre, Centre Hospitalier Universitaire de Lille, Lille, France.
ULR2694-METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, Axe Environnement Périnatal et Santé, Centre Hospitalier Universitaire de Lille, Lille, France.
Front Pediatr. 2023 Sep 6;11:1236556. doi: 10.3389/fped.2023.1236556. eCollection 2023.
Congenital diaphragmatic hernia (CDH) is a rare condition characterized by pulmonary hypoplasia, vascular dystrophy, and pulmonary hypertension at birth. Validation of the lamb model as an accurate representation of human CDH is essential to translating research findings into clinical practice and understanding disease mechanisms. This article emphasizes the importance of validating the lamb model to study CDH pathogenesis and develop innovative therapeutics.
At 78 days of gestation, the fetal lamb's left forelimb was exposed through a midline laparotomy and hysterotomy, and a supra diaphragmatic thoracotomy was performed to allow the digestive organs to ascend into the thoracic cavity. At 138 ± 3 days of gestation, lambs were delivered via a cesarean section; then, with umbilical cord intact during 1 hour, the lambs were mechanically ventilated with gentle ventilation in a pressure-controlled mode for 2 h.
CDH lambs exhibited a lower left lung-to-body weight ratio of 5.3 (2.03), < 0.05, and right lung-to-body weight ratio of 8.2 (3.1), < 0.05. They reached lower Vt/kg (tidal volume per kg) during the course of the resuscitation period with 1.2 (0.7) ml/kg at 10 min and 3 (1.65) ml/kg at 60 min ( < 0.05). Compliance of the respiratory system was lower in CDH lambs with 0.5 (0.3) ml/cmHO at 60 min ( < 0.05) and 0.9 (0.26) ml/cmHO at 120 min ( < 0.05). Differences between pre- and postductal SpO were higher with 15.1% (21.4%) at 20 min and 6.7% (14.5%) at 80 min ( < 0.05). CDH lambs had lower differences between inspired and expired oxygen fractions with 4.55% (6.84%) at 20 min and 6.72% (8.57%) at 60 min ( < 0.05). CDH lamb had lower left ventricle [2.73 (0.5) g/kg, < 0.05] and lower right ventricle [0.69 (0.8), < 0.05] to left ventricle ratio.
CDH lambs had significantly lower tidal volume than control lambs due to lower compliance of the respiratory system and higher airway resistance. These respiratory changes are characteristic of CDH infants and are associated with higher mortality rates. CDH lambs also exhibited pulmonary hypertension, pulmonary hypoplasia, and left ventricle hypoplasia, consistent with observations in human newborns. To conclude, our lamb model successfully provides a reliable representation of CDH and can be used to study its pathophysiology and potential interventions.
先天性膈疝（CDH）是一种罕见病症，其特征为出生时肺发育不全、血管营养不良和肺动脉高压。验证羔羊模型能否准确模拟人类CDH对于将研究成果转化为临床实践以及理解疾病机制至关重要。本文强调了验证羔羊模型以研究CDH发病机制和开发创新疗法的重要性。
在妊娠78天时，通过中线剖腹术和子宫切开术暴露胎羊的左前肢，并进行膈上开胸术，以使消化器官升入胸腔。在妊娠138±3天时，通过剖宫产分娩羔羊；然后，在脐带完整的情况下，在1小时内对羔羊进行压力控制模式下的轻柔机械通气2小时。
患有CDH的羔羊左肺与体重之比更低，为5.3（2.03），<0.05，右肺与体重之比为8.2（3.1），<0.05。在复苏期，它们达到的每千克潮气量（Vt/kg）更低，10分钟时为1.2（0.7）毫升/千克，60分钟时为3（1.65）毫升/千克（<0.05）。CDH羔羊的呼吸系统顺应性更低，60分钟时为0.5（0.3）毫升/厘米水柱（<0.05），120分钟时为0.9（0.26）毫升/厘米水柱（<0.05）。导管前和导管后血氧饱和度（SpO）之间的差异更高，20分钟时为15.1%（21.4%），80分钟时为6.7%（14.5%）（<0.05）。CDH羔羊吸入和呼出氧分数之间的差异更低，20分钟时为4.55%（6.84%），60分钟时为6.72%（8.57%）（<0.05）。CDH羔羊的左心室[2.73（0.5）克/千克，<0.05]和右心室与左心室的比率更低[0.69（0.8），<0.05]。
由于呼吸系统顺应性较低和气道阻力较高，患有CDH的羔羊潮气量明显低于对照羔羊。这些呼吸变化是CDH婴儿的特征，并且与较高的死亡率相关。CDH羔羊还表现出肺动脉高压、肺发育不全和左心室发育不全，这与人类新生儿的观察结果一致。总之，我们的羔羊模型成功地提供了CDH的可靠模型，可用于研究其病理生理学和潜在干预措施。
