重度特发性肺动脉高压患者外周血管内皮功能受损与肺血管对吸入伊洛前列素的反应相关。

Impaired peripheral endothelial function in severe idiopathic pulmonary hypertension correlates with the pulmonary vascular response to inhaled iloprost.

作者信息

Wolff Birger, Lodziewski Sven, Bollmann Tom, Opitz Christian F, Ewert Ralf

机构信息

Department of Cardiology, Franz-Volhard-Klinik Berlin, Charitè Campus Buch, HELIOS Kliniken Berlin, Berlin, Germany.

出版信息

Am Heart J. 2007 Jun;153(6):1088.e1-7. doi: 10.1016/j.ahj.2007.03.005.

DOI:10.1016/j.ahj.2007.03.005

PMID:17540215

Abstract

BACKGROUND

Pulmonary endothelial function is known to be impaired in subjects with idiopathic pulmonary arterial hypertension (IPAH), but peripheral endothelial dysfunction and its predictive value for pulmonary vasoreactivity have not been previously investigated.

METHODS

Measurements of peripheral endothelium-dependent and endothelium-independent vasoreactivity using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation of the brachial artery were performed in 18 patients with severe IPAH (15 women; mean age 50 years [95% confidence interval 46-55 years], mean pulmonary artery pressure [PAP] 51 mm Hg [43-59 mm Hg], pulmonary vascular resistance [PVR] 1239 dyn s cm(-5) [861-1618 dyn s cm(-5)] at baseline) and in 36 age- and sex-matched controls. In patients with IPAH, acute pulmonary vasoreactivity was measured as pulmonary vascular response to inhaled iloprost (PVRII) during pulmonary catheterization.

RESULTS

Compared to controls, patients with IPAH demonstrated impaired peripheral endothelial function (FMD, 0.19 [0.07-0.31] vs 0.38 [0.30-0.44] mm among controls; P =.002). No such impairment was observed for nitroglycerin-mediated dilation (0.34 [0.23-0.46] vs 0.36 [0.20-0.51] mm among controls; P = .679). Among patients with IPAH, iloprost lowered mean PAP by 8.2 mm Hg (2.0-14.5 mm Hg) (P = .001) and PVR by 395 dyn s cm(-5) (109-680 dyn s cm(-5)) (P < .001). Subsequent analysis of the association between peripheral endothelial function and PVRII disclosed a correlation of FMD with the percent decrease in mean PAP (r = .65, P = .003) and PVR (r = 0.67, P = .002), in which patients with IPAH with the greatest PVRII also exhibited the highest FMD values.

CONCLUSIONS

Idiopathic pulmonary arterial hypertension is associated with peripheral endothelial dysfunction. Peripheral endothelium-dependent vasoreactivity correlates with the PVRII. It remains to be established if FMD has the potential as a clinical tool for noninvasive estimation of pulmonary vasoreactivity in IPAH.

摘要

背景

已知特发性肺动脉高压（IPAH）患者存在肺内皮功能受损，但此前尚未研究外周内皮功能障碍及其对肺血管反应性的预测价值。

方法

对18例重度IPAH患者（15例女性；平均年龄50岁[95%置信区间46 - 55岁]，基线时平均肺动脉压[PAP]51 mmHg[43 - 59 mmHg]，肺血管阻力[PVR]1239 dyn s cm⁻⁵[861 - 1618 dyn s cm⁻⁵]）和36例年龄及性别匹配的对照者进行外周内皮依赖性和非内皮依赖性血管反应性测量，采用肱动脉血流介导的舒张功能（FMD）和硝酸甘油介导的舒张功能检测。在IPAH患者中，急性肺血管反应性通过肺动脉导管插入术期间吸入伊洛前列素（PVRII）后的肺血管反应来测量。

结果

与对照组相比，IPAH患者外周内皮功能受损（FMD，对照组为0.38[0.30 - 0.44]mm，IPAH患者为0.19[0.07 - 0.31]mm；P = 0.002）。硝酸甘油介导的舒张功能未观察到此类损害（对照组为0.36[0.20 - 0.51]mm，IPAH患者为0.34[0.23 - 0.46]mm；P = 0.679）。在IPAH患者中，伊洛前列素使平均PAP降低8.2 mmHg（2.0 - 14.5 mmHg）（P = 0.001），使PVR降低395 dyn s cm⁻⁵（109 - 680 dyn s cm⁻⁵）（P < 0.001）。随后对外周内皮功能与PVRII之间的关联进行分析，发现FMD与平均PAP降低百分比（r = 0.65，P = 0.003）和PVR（r = 0.67，P = 0.00）相关，其中PVRII最大的IPAH患者FMD值也最高。