From the State Key Laboratory of Cardiovascular Diseases and Center for Pediatric Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases (Y.H., Y.-W.L., X.-L.Z., J.L., L.X., J.M., P.-H.W., H.Z.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
Children's Heart Center, the Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Zhejiang, China (H.-Z.P.).
Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):704-718. doi: 10.1161/ATVBAHA.118.311992.
Objective- Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and persistently elevated mean pulmonary artery pressures and pulmonary vascular resistance. We aimed to investigate whether transthoracic pulmonary artery denervation (TPADN) attenuated pulmonary artery (PA) remodeling, improved right ventricular (RV) function, and affected underlying mechanisms. We also explored the distributions of sympathetic nerves (SNs) around human PAs for clinical translation. Approach and Results- We identified numerous SNs in adipose and connective tissues around the main PA trunks and bifurcations in male Sprague Dawley rats, which were verified in samples from human heart transplant patients. Pulmonary arterial hypertensive rats were randomized into TPADN and sham groups. In the TPADN group, SNs around the PA trunk and bifurcation were completely and accurately removed under direct visualization. The sham group underwent thoracotomy. Hemodynamics, RV function, and pathological changes in PA and RV tissues were measured via right heart catheterization, cardiac magnetic resonance imaging, and pathological staining, respectively. Compared with the sham group, the TPADN group had lower mean pulmonary arterial pressures, less PA and RV remodeling, and improved RV function. Furthermore, TPADN inhibited neurohormonal overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system and regulated abnormal expressions and signaling of neurohormone receptors in local tissues. Conclusions- There are numerous SNs around the rat and human main PA trunks and bifurcations. TPADN completely and accurately removed the main SNs around PAs and attenuated pulmonary arterial hypertensive progression by inhibiting excessive activation of the sympathetic nervous system and renin-angiotensin-aldosterone system neurohormone-receptor axes.
肺动脉高压的特征是进行性肺血管重构，持续升高的平均肺动脉压和肺血管阻力。我们旨在研究经胸肺动脉去神经支配（TPADN）是否能减轻肺动脉（PA）重构、改善右心室（RV）功能，并影响潜在机制。我们还探索了人类 PA 周围交感神经（SNs）的分布，以促进临床转化。
我们在雄性 Sprague Dawley 大鼠的主肺动脉干和分叉处的脂肪和结缔组织中发现了大量的 SNs，这在人类心脏移植患者的样本中得到了验证。肺动脉高压大鼠被随机分为 TPADN 和假手术组。在 TPADN 组中，SNs 围绕肺动脉干和分叉在直视下被完全准确地去除。假手术组接受了开胸手术。通过右心导管检查、心脏磁共振成像和病理染色分别测量血流动力学、RV 功能以及 PA 和 RV 组织的病理变化。与假手术组相比，TPADN 组的平均肺动脉压较低，PA 和 RV 重构较少，RV 功能改善。此外，TPADN 抑制了交感神经系统和肾素-血管紧张素-醛固酮系统的神经激素过度激活，并调节了局部组织中神经激素受体的异常表达和信号。
大鼠和人类的主肺动脉干和分叉周围有大量的 SNs。TPADN 通过抑制交感神经系统和肾素-血管紧张素-醛固酮系统神经激素受体轴的过度激活，完全准确地去除了 PA 周围的主要 SNs，从而减轻了肺动脉高压的进展。
