Stenbøg E V, Steinbrüchel D A, Thomsen A B, Baandrup U, Heickendorff L, Ingerslev J, Andersen N T, Emmertsen K
Dept of Cardiothoracic Surgery, Aarhus University Hospital, Denmark.
Cardiol Young. 2001 Jul;11(4):420-30. doi: 10.1017/s1047951101000543.
Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal models which reflect the disease process.
We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In both groups, histomorphometry revealed markedly increased muscularity of the intra-acinar pulmonary arteries. Circulating levels of endothelin were normal in the shunted animals, and elevated in those with ligation of the left pulmonary artery.
In neonatal porcine models of pulmonary vascular disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascular disease in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations.
先天性心脏畸形情况下的高血压和肺血管床的高灌注可能会导致进行性肺血管疾病。为了更好地理解这种疾病的基本机制，需要有反映疾病过程的临床相关动物模型。
我们将45只出生48小时的新生猪随机分组，其中9只进行3毫米中央主-肺动脉分流术，13只进行左肺动脉结扎术。对照组包括13只假手术组和10只未手术组。随访持续三个月。大多数猪的干预措施与存活情况相符。分流术导致收缩期肺动脉压急性升高85%，肺血流量增加两倍多。到三个月大时，几乎所有分流术都已自发闭合，血流动力学恢复正常。左肺动脉结扎术导致尽管只有右肺灌注，但总肺血流量正常，收缩期肺动脉压升高33%。这些血流动力学变化在整个研究期间持续存在。两组中，组织形态计量学显示腺泡内肺动脉的肌层明显增厚。分流动物体内内皮素的循环水平正常，而左肺动脉结扎动物体内的内皮素水平升高。
在通过构建3毫米中央主-肺动脉分流术和结扎一条肺动脉建立的新生猪肺血管疾病模型中，我们观察到肺血管的组织病理学变化类似于人类早期高血压性肺血管疾病。内皮素循环水平升高与异常血流动力学相关，而非与异常病理学相关。这些发现对于未来研究与先天性心脏畸形相关的高血压性肺血管疾病的发病机制可能具有重要价值。
