Reddy V M, Meyrick B, Wong J, Khoor A, Liddicoat J R, Hanley F L, Fineman J R
Department of Cardiothoracic Surgery, University of California San Francisco, 94143-0106, USA.
Circulation. 1995 Aug 1;92(3):606-13. doi: 10.1161/01.cir.92.3.606.
The development of pulmonary hypertension and its associated increased vascular reactivity is a common accompaniment of congenital heart disease with increased pulmonary blood flow. Although the morphology of the pulmonary vascular changes is well described, the mechanisms of vascular remodeling and increased reactivity remain incompletely understood.
To elucidate these mechanisms, we established an accurate and reliable experimental model of pulmonary hypertension with increased pulmonary blood flow. An aortopulmonary shunt was created with an 8.0-mm expanded polytetrafluoroethylene vascular graft in 11 late-gestation fetal lambs. At 1 month of age, shunted lambs had a pulmonary-to-systemic blood flow ratio of 2.2 +/- 1.2. Compared with 11 age-matched control lambs, mean pulmonary arterial pressure (44.8 +/- 11.7 versus 16.2 +/- 2.9 mm Hg) and the ratio of pulmonary to systemic arterial pressure were significantly increased (P < .05). Pulmonary vascular resistance was not significantly increased. The pulmonary vasoconstricting response to the infusion of U46619 (a thromboxane A2 mimic) or acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy, abnormal extension of muscle distally into the walls of the intra-acinar arteries, and increased numbers of barium-filled intra-acinar arteries.
In utero placement of aortopulmonary shunts reproduces the aberrant hemodynamic state of children with cogenital heart disease with left-to-right shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and vascular remodeling. In addition, the lambs have a unique paradoxical increase in pulmonary vascular volume that attenuates an increase in pulmonary vascular resistance. This experimental preparation provides a useful and consistent model for the study of the pathogenesis of pulmonary hypertension.
肺动脉高压的发展及其相关的血管反应性增加是先天性心脏病伴肺血流量增加的常见伴随情况。尽管肺血管变化的形态已得到充分描述，但血管重塑和反应性增加的机制仍未完全了解。
为阐明这些机制，我们建立了一个准确可靠的肺血流量增加的肺动脉高压实验模型。在11只妊娠晚期胎羊中，用8.0毫米的膨体聚四氟乙烯血管移植物建立了主肺动脉分流。在1月龄时，分流胎羊的肺循环与体循环血流量之比为2.2±1.2。与11只年龄匹配的对照胎羊相比，平均肺动脉压（44.8±11.7对16.2±2.9毫米汞柱）和肺循环与体循环动脉压之比显著升高（P<.05）。肺血管阻力没有显著增加。分流胎羊对输注U46619（一种血栓素A2类似物）或急性肺泡缺氧的肺血管收缩反应也增强。对钡剂充盈的肺动脉床进行形态计量分析显示，中膜肥厚，肌肉异常向远端延伸至腺泡内动脉壁，钡剂充盈的腺泡内动脉数量增加。
在子宫内放置主肺动脉分流可重现先天性心脏病左向右分流患儿的异常血流动力学状态；出生后肺动脉高压、肺血流量增加和血管重塑。此外，胎羊的肺血管容量有独特的反常增加，这减弱了肺血管阻力的增加。这种实验准备为研究肺动脉高压的发病机制提供了一个有用且一致的模型。
