Pulmonary Artery Denervation Attenuates Pulmonary Arterial Remodeling in Dogs With Pulmonary Arterial Hypertension Induced by Dehydrogenized Monocrotaline
Pulmonary Artery Denervation Attenuates Pulmonary Arterial Remodeling in Dogs With Pulmonary Arterial Hypertension Induced by Dehydrogenized Monocrotaline
复制标题
DOI：
10.1016/j.jcin.2015.09.015
复制
发表时间：
2015-12-28
影响因子：
11.3
通讯作者：
Chen, Shao-Liang
中科院分区：
文献类型：
--
作者：
Zhou, Ling;Zhang, Juan;Chen, Shao-Liang
本研究旨在探讨肺动脉去神经（pulmonary arterial denervation，PADN）对肺动脉高压（pulmonary arterial hypertension，PAH）动物交感神经（sympathetic nerve，SN）超微结构、血流动力学和肺动脉（pulmonary artery，PA）病理的影响及其机制。以往的研究报道，短期改善肺动脉压（PAP）和心功能的PADN，但PA重塑和相关的机制尚不清楚。方法40只犬随机（1：3的比例）分配到对照组（心房内注射N-二甲基乙酰胺，3 mg/kg）和试验组（心房内注射野百合碱，3 mg/kg）。8周后，将平均PAP > 25 mm Hg的试验组动物（n = 20）随机（1：1比例）分为假手术组和PADN组。14周时测定肺血流动力学、肺动脉中膜厚度、PA肌化程度及肺组织mRNA表达。结果PADN可引起SN髓鞘脱失和轴突缺失，使SN传导速度减慢，平均PAP显著降低（23.5 +/- 2.3 mm Hg vs. 33.7 +/- 5.8 mm Hg），肺血管阻力（3.5 +/- 2.3木材单位vs. 7.7 +/- 1.7木材单位），内侧壁厚度（22.3 ± 3.3% vs. 30.4 ± 4.1%），和充分的肌肉化（40.3 +/- 9.3% vs. 57.1 +/- 5.7%）和增加的非肌化（29.8 +/- 6.1% vs. 12.9 +/- 4.9%）（均p < 0.001）。PADN抑制信使核糖核酸表达的基因相关的炎症，增殖，和vascortization.CONCLUSIONS PADN诱导永久性SN损伤和随后的改善血液动力学和PA重塑PAH动物通过机制，可能是实验和临床有益的。(C)2015年由美国心脏病学会基金会。
OBJECTIVES This study aimed to investigate sympathetic nerve (SN) ultrastructural changes and hemodynamic and pulmonary artery (PA) pathological improvements by pulmonary arterial denervation (PADN) in animals with pulmonary arterial hypertension (PAH), as well as the underlying mechanisms.BACKGROUND SN overactivity plays a role in PAH. Previous studies have reported short-term improvements in pulmonary arterial pressure (PAP) and cardiac function by PADN, but PA remodeling and the associated mechanisms remain unclear.METHODS Forty dogs were randomly (ratio of 1: 3) assigned to the control (intra-atrial injection of N-dimethylacetamide, 3 mg/kg) and test (intra-atrial injection of dehydrogenized-monocrotaline, 3 mg/kg) groups. After 8 weeks, the animals in the test group with a mean PAP > 25 mm Hg (n = 20) were randomized (ratio of 1: 1) into the sham and PADN groups. At 14 weeks, the hemodynamics, medial wall thickness and PA muscularization, and messenger ribonucleic acid expression of genes in lung tissues were measured. Another 35 PAH dogs were used to measure the SN conduction velocity, electron microscopic assessment, and nerve distribution.RESULTS PADN induced significant SN demyelination and axon loss and slowed SN conduction velocity over time, with resulting profound reductions in the mean PAP (23.5 +/- 2.3 mm Hg vs. 33.7 +/- 5.8 mm Hg), pulmonary vessel resistance (3.5 +/- 2.3 Wood units vs. 7.7 +/- 1.7 Wood units), medial wall thickness (22.3 +/- 3.3% vs. 30.4 +/- 4.1%), and full muscularization (40.3 +/- 9.3% vs. 57.1 +/- 5.7%) and increased nonmuscularization (29.8 +/- 6.1% vs. 12.9 +/- 4.9%) compared with the Sham group (all p < 0.001). PADN inhibited the messenger ribonucleic acid expression of genes correlated with inflammation, proliferation, and vasoconstriction.CONCLUSIONS PADN induces permanent SN injury and subsequent improvements in hemodynamics and PA remodeling in animals with PAH through mechanisms that may be experimentally and clinically beneficial. (C) 2015 by the American College of Cardiology Foundation.