Schmidt Augusto Frederico, Rojas-Moscoso Julio Alejandro, Gonçalves Frances Lilian Lanhellas, Gallindo Rodrigo Melo, Mónica Fabíola Zakia, Antunes Edson, Figueira Rebeca Lopes, Sbragia Lourenço
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Pediatr Surg Int. 2013 May;29(5):489-94. doi: 10.1007/s00383-012-3238-8. Epub 2012 Dec 27.
Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage and a significant cause of morbidity and mortality. Our aim was to study the pulmonary artery reactivity in an animal model of CDH.
To investigate the reactivity of the aorta and left pulmonary artery in a rabbit model of CDH, we studied the in vitro responses to the α1-adrenoceptor agonist phenylephrine (PE) and to both the muscarinic receptor agonist (ACh) and the nitric oxide (NO) donor sodium nitroprusside (SNP). Rabbits underwent surgery at 25 days of gestation. CDH was created in one fetus per horn (n = 8). Remaining fetuses were considered controls (n = 18). At term (30 days), the lung, left pulmonary artery, and aorta were dissected. In a separate group, endothelium was mechanically removed.
There were no differences in the contractile and relaxing responses of aorta in all groups. In left pulmonary artery, PE-induced contractions were significantly greater (p < 0.05) in CDH when compared with control group. The increased responsiveness to PE in CDH group was similar to that found in pulmonary artery without endothelium. The ACh-induced pulmonary artery relaxation was markedly reduced in CDH when compared with control group (p < 0.05), whereas no differences were found for SNP.
Our results show increased contractility and impairment in endothelium-dependent relaxation of pulmonary artery in CDH, mimicking an endothelial dysfunction, with preserved response to endothelium-independent mechanism.
先天性膈疝（CDH）与肺动脉高压相关，肺动脉高压常常难以控制，是发病和死亡的重要原因。我们的目的是在CDH动物模型中研究肺动脉反应性。
为了研究CDH兔模型中主动脉和左肺动脉的反应性，我们研究了对α1肾上腺素能受体激动剂去氧肾上腺素（PE）、毒蕈碱受体激动剂（ACh）和一氧化氮（NO）供体硝普钠（SNP）的体外反应。兔子在妊娠25天时接受手术。每个子宫角的一个胎儿制造CDH（n = 8）。其余胎儿作为对照组（n = 18）。足月时（30天），解剖肺、左肺动脉和主动脉。在另一组中，机械去除内皮。
所有组中主动脉的收缩和舒张反应没有差异。在左肺动脉中，与对照组相比，CDH组中PE诱导的收缩明显更大（p < 0.05）。CDH组中对PE反应性的增加与无内皮的肺动脉中发现的情况相似。与对照组相比，CDH组中ACh诱导的肺动脉舒张明显降低（p < 0.05），而SNP方面未发现差异。
我们的结果显示，CDH中肺动脉的收缩性增加且内皮依赖性舒张受损，模拟了内皮功能障碍，而对非内皮依赖性机制的反应保留。
