Laboratoire de Recherche Chirurgicale and INSERM U999, Hôpital Marie Lannelongue, Université Paris Sud, Le Plessis Robinson, France.
J Thorac Cardiovasc Surg. 2012 Apr;143(4):967-73. doi: 10.1016/j.jtcvs.2011.12.052. Epub 2012 Jan 27.
The study objective was to determine whether the vasculopathy seen in nonobstructed lung regions in chronic thromboembolic pulmonary hypertension is induced by the local blood flow increase or by factors released by the ischemic lung.
Three groups of 10 piglets were studied 5 weeks after right pulmonary artery ligation, right pneumonectomy, or right pulmonary artery dissection (sham). Pulmonary vascular resistance, pulmonary arterial vasoreactivity, and morphometry were measured, and gene expressions of factors involved in vascular smooth muscle cell proliferation were quantified.
Left lung blood flow was similarly increased after right pneumonectomy and right pulmonary artery ligation. Compared with right pneumonectomy, right pulmonary artery ligation resulted in left lung vasculopathy with increased pulmonary vascular resistance (P = .0009), medial hypertrophy of the distal pulmonary artery (P < .0001), and decreases in maximal relaxation to acetylcholine (P = .013) and endothelial nitric oxide synthase gene expression (P = .041). These values were similar after sham and right pneumonectomy. In the left lung, right pulmonary artery ligation increased the gene expressions for insulin-like growth factor (P = .034), platelet-derived growth factor (P = .0006), and vascular endothelial growth factor (P = .0105) compared with right pneumonectomy and sham. Whereas endothelin-1 gene expression was not affected, expressions of endothelin-1 receptors A and B were downregulated after right pneumonectomy (P = .048 and P = .039, respectively) and right pulmonary artery ligation (P = .033 and P = .028, respectively).
Pulmonary vasculopathy was absent in the remaining lung 5 weeks after right pneumonectomy but developed in the nonobstructed lung regions 5 weeks after right pulmonary artery ligation, suggesting that factors released by the ischemic lung induced vascular remodeling in the contralateral lung. This endocrine process may involve the release of factors involved in vascular smooth muscle cell proliferation.
本研究旨在确定慢性血栓栓塞性肺动脉高压中无阻塞肺区的血管病变是由局部血流增加引起的，还是由缺血肺释放的因子引起的。
研究了右肺动脉结扎、右肺切除或右肺动脉夹层（假手术）后 5 周的 3 组 10 头小猪。测量了肺血管阻力、肺动脉血管反应性和形态计量学，并定量了参与血管平滑肌细胞增殖的因子的基因表达。
右肺切除和右肺动脉结扎后，左肺血流量相似增加。与右肺切除相比，右肺动脉结扎导致左肺血管病变伴肺血管阻力增加（P =.0009）、远端肺动脉中膜肥厚（P <.0001）和乙酰胆碱最大松弛度降低（P =.013）和内皮型一氧化氮合酶基因表达降低（P =.041）。假手术和右肺切除后，这些值相似。在左肺中，与右肺切除和假手术相比，右肺动脉结扎增加了胰岛素样生长因子（P =.034）、血小板衍生生长因子（P =.0006）和血管内皮生长因子（P =.0105）的基因表达。内皮素-1 基因表达不受影响，而内皮素-1 受体 A 和 B 的表达在右肺切除（P =.048 和 P =.039）和右肺动脉结扎（P =.033 和 P =.028）后下调。
右肺切除后 5 周，剩余肺无肺血管病变，但右肺动脉结扎后 5 周，非阻塞肺区出现肺血管病变，提示缺血肺释放的因子诱导对侧肺血管重塑。这个内分泌过程可能涉及参与血管平滑肌细胞增殖的因子的释放。
