增加肺动脉脉动流改善缺氧性肺动脉高压的仔猪
Summary
Pulmonary hypertension is associated with a significant reduction in pulmonary artery pulsatility, contractility and elasticity, contributing to an increase in pulmonary artery pressure and pulmonary resistance. Using a hypoxic piglet model, this study demonstrated that improving pulmonary artery plasticity using a newly developed pulsatile catheter improves hypoxic pulmonary hypertension.
Abstract
肺动脉高压（PAH）是一种疾病，影响远端肺动脉（PA）。这些动脉发生变形，导致右心衰竭。目前的治疗是有限的。生理学上，脉动血流是不利的脉管。响应于持续脉动应力，血管释放一氧化氮（NO）来诱导血管舒张自我保护。基于这一观察，本研究开发的协议，以评估一个人工肺脉动血流是否能诱导肺动脉压的编号为依赖性减少。一组小猪暴露于慢性缺氧3周和相比仔猪的对照组。每周一次，仔猪进行超声心动图检查，以评估PAH的严重程度。在缺氧暴露结束时，仔猪经使用一种脉动导管脉动协议。之后被麻醉并为手术准备，仔猪的颈静脉分离并在CAtheter通过右心房，右心室和肺动脉，下放射线控制引入。肺动脉压（PAP）的前（T0）测定，（T1）和后（T 2）的搏动协议30分钟后立即使用。已证明，这种脉动协议是经由NO依赖性机制诱导显著减少平均PAP的安全和有效的方法。这些数据开辟PAH的临床管理的新途径。
Introduction
肺动脉高血压是一种威胁生命的疾病，影响肺血管。有协议认为增加血管收缩剂（内皮素，血清素）和血管扩张剂的减少（NO，前列环素）之间的不平衡有助于PAH的发展领域。随着时间的推移，这种亲缩窄型演变成一个复杂的亲增殖和抗凋亡表型，促进血管病变的发展1。
长时间暴露于血管收缩导致的[Ca 2+]一个显著和持续增加i的肺动脉平滑肌细胞，允许几个钙调节转录因子，如NFAT 2-4的活化，促进PASMC增殖和耐一细胞凋亡表型5。这种表型导致肺血管病变，有助于增加在两个PA压和肺动脉水库istance，最终导致致命右心脏衰竭6。
目前，存在着逆转PAH虽然有几个是改善生活7患者的生存质量提供任何治疗。在这些处理中，吸入NO治疗的有效性已经被证实，但由于其半衰期短的，很难在临床实践中使用。出于这个原因，更稳定和持久的治疗方法已被优选的，如前列环素类似物，或内皮素受体 阻断剂7。为了开发更好的治疗方法，有必要改进和扩大PAH的病理生理学的知识。
搏动是公知的刺激激活切应力诱发的血管扩张，保护从高压侧流损伤8,9-非弹性远端动脉。在PAH的二次模型来体肺分流手术，努尔等证明肺内剪STRESS介导的血管内皮功能的增强10。几个研究已经证明，NO，前列环素和ET-1的表达是紧密的变化脉动流调节。实际上，适度增加脉动流增加eNOS活性和前列环素的水平，这两者都降低了肺动脉高压。脉动流调制可能牵连PAH的病因和人为地增加这是一个有吸引力的和新颖的肺循环中增加NO和前列环素的生产方式。
本研究旨在评估10分钟搏动的影响，用流动的血流动力学测量了新开发的脉动导管在肺动脉高压（PH）模型在仔猪在其中缺氧已致。据推测，增加肺动脉搏动引起肺动脉的血管舒张，因此降低肺动脉压力。
右心脏猫heterization（RHC）是诊断的关键临床干预和随访PAH患者。事实上，它是诊断肺动脉高压，并允许医生评估血管反应性11,12以及疾病进展的最可靠的方法。其实每一个PAH患者接受RHC几次。本研究在大型动物的目的是展示脉动导管的疗效和安全性评估和有规律RHC过程期间处理的PAH。因为脉动导管已经上市和RHC是在PAH患者常规进行，该研究提供了所有能够迅速进行临床试验所需的信息。
Protocol
Representative Results
Discussion
对于第一次，它已被证明其在变化肺脉动流被因果相关的PAH的继发慢性缺氧暴露的发展。这种转换方法提供的证据表明诱导人工增加使用一个特别设计的导管肺脉动流改善肺动脉高血压，可能是通过增加NO的产生。
这些发现不仅原来，他们是伟大的治疗意义也证明了内源性NO的产生可以机械，安全地刺激了肺循环中，而不会影响系统的功能。研究设计符合最新的临床前研究建?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
The authors have nothing to disclose.
Materials
| Drugs for anesthesia | |||
| sodium thiopental, THIOPENTAL SODIUM | Abbott, France | 0000071-73-8 | powder 3 place Gustave Eiffe 94518 RUNGIS CEDEX. |
| isoflurane, FORANE | Abbott, France | 05260-05 | glass bottle 250 ml 3 place Gustave Eiffe 94518 RUNGIS CEDEX. |
| midazolam, Hypnovel | Accord Healthcare | Vidal | injectable ampoules 1mg/ml 45 Rue du Faubourg de Roubaix 59000 Lille France |
| pramocaine,TRONOTHANE 1 % | Laboratoires LISAPHARM | Vidal | Gel appl locale T/30g 3, rue Scheffer. 75016 Paris. |
| morphine chlohydrate Lavoisier | CMD Lavoisier Laboratoires CHAIX et DU MARAIS | Vidal | injectable ampoules 7, rue Labie -75017 Paris – France |
| Acrylates Copolymer-Carbopol® Aqua SF-1 Polymer | Lubrizol | gel appl local Elysées La Défense 19 le Parvis 92073 Paris la défense |
|
| Material | |||
| Ventilateur Harvard 683 | Harvard apparatus | Harvard apparatus | DRIM 75 rue des Anglais – 78700 Conflans Ste Honorine |
| Echographe Voluson E8 with a 3,5 MHz probe | General Electric | GEHealthcare | DRIM 75 rue des Anglais – 78700 Conflans Ste Honorine |
| Pulsatil Catheter | Cardio inovating system | Cardio innovative systems, 33 rue Vivienne, Paris, France 75002 | |
| NO breath Analyseur | Respur | Respur | 26 rue Felix Rouget 95490 Vaureal France |
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