Flemmer Andreas W, Jani Jacques C, Bergmann Florian, Muensterer Oliver J, Gallot Denis, Hajek Kerstin, Sugawara Junichi, Till Holger, Deprest Jan A
Division of Neonatology, University Children's Hospital, Perinatal Center, Ludwig-Maximilian-University Munich, Grosshadern, Germany.
Pediatr Pulmonol. 2007 Jun;42(6):505-12. doi: 10.1002/ppul.20618.
Several animal models have been proposed to study the pathophysiology of congenital diaphragmatic hernia (CDH). Surgical induction of CDH in fetal rabbits during the pseudoglandular phase has been shown to induce severe pulmonary hypoplasia, but functional studies in this model are scarce. We aimed to measure neonatal pulmonary impedance and related it to the severity of lung hypoplasia. CDH was surgically created in rabbits at 23 days of gestation. Following cesarean delivery at term (31 days) pups were subjected to measurement of total lung capacity (TLC), lung to body weight ratio (LBWR) and lung impedance by forced oscillation technique (FOT). Airway resistance (R(aw)), tissue elastance (H(L)), tissue damping (G(L)), and hysteresivity (eta) (G(L)/H(L)) were calculated from impedance data. Twelve CDH fetuses and 15 controls were available for final analysis. LBWR and TLC were significantly lower in the CDH group compared to gestational and age matched controls (P<0.001). R(aw), H(L), and G(L) were significantly increased in CCDH fetuses. eta and H(L) best reflected lung hypoplasia (LBWR) (r(2) = 0.42 and 0.43; P=0.001), indicating a dominant contribution of lung tissue mechanics to CDH-induced lung hypoplasia. We successfully introduced lung impedance measurement by FOT in neonatal rabbits. Following surgical induction of CDH in the pseudoglandular phase, they have, next to morphological evidence of pulmonary hypoplasia, changes in lung mechanics. Our results for lung tissue mechanics support the concept of delayed pulmonary tissue modeling. We propose to employ functional studies in future experiments when evaluating prenatal interventions aimed at reversing pulmonary hypoplasia.
已经提出了几种动物模型来研究先天性膈疝（CDH）的病理生理学。在假腺期对胎兔进行CDH手术诱导已被证明可导致严重的肺发育不全，但该模型的功能研究较少。我们旨在测量新生兔的肺阻抗，并将其与肺发育不全的严重程度相关联。在妊娠23天时通过手术在兔中制造CDH。足月（31天）剖宫产术后，对幼崽进行总肺容量（TLC）、肺与体重比（LBWR）的测量，并通过强迫振荡技术（FOT）测量肺阻抗。根据阻抗数据计算气道阻力（R(aw)）、组织弹性（H(L)）、组织阻尼（G(L)）和滞后率（eta）（G(L)/H(L)）。12只CDH胎儿和15只对照可用于最终分析。与妊娠和年龄匹配的对照相比，CDH组的LBWR和TLC显著降低（P<0.001）。CDH胎儿的R(aw)、H(L)和G(L)显著增加。eta和H(L)最能反映肺发育不全（LBWR）（r(2)=0.42和0.43；P=0.001），表明肺组织力学对CDH诱导的肺发育不全起主要作用。我们成功地在新生兔中引入了通过FOT测量肺阻抗的方法。在假腺期手术诱导CDH后，除了肺发育不全的形态学证据外，它们的肺力学也发生了变化。我们关于肺组织力学的结果支持肺组织建模延迟的概念。我们建议在未来的实验中，在评估旨在逆转肺发育不全的产前干预措施时采用功能研究。
