Christie Jason D, Robinson Nancy, Ware Lorraine B, Plotnick Michael, De Andrade Joao, Lama Vibha, Milstone Aaron, Orens Jonathan, Weinacker Ann, Demissie Ejigayehu, Bellamy Scarlett, Kawut Steven M
Division of Pulmonary, Allergy, and Critical Care Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Am J Respir Crit Care Med. 2007 Jan 1;175(1):69-74. doi: 10.1164/rccm.200606-827OC. Epub 2006 Oct 5.
Acute lung injury is characterized by hypercoagulability and impaired fibrinolysis. We hypothesized that lower protein C and higher type 1 plasminogen activator inhibitor (PAI-1) levels in plasma would be associated with primary graft dysfunction (PGD) after lung transplantation.
Prospective, multicenter cohort study.
We measured plasma levels of protein C and PAI-1 before lung transplantation and 6, 24, 48, and 72 h after allograft reperfusion in 128 lung transplant recipients at six centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) 72 h after transplantation. Biomarker profiles were evaluated using logistic regression and generalized estimating equations.
Patients who developed PGD had lower protein C levels 24 h posttransplantation than did patients without PGD (mean +/- SD [relative to control]: 64 +/- 27 vs. 92 +/- 41%, respectively; p = 0.002). Patients with PGD also had PAI-1 levels that were almost double those of patients without PGD at 24 h (213 +/- 144 vs. 117 +/- 89 ng/ml, respectively; p < 0.001). Throughout the 72-h postoperative period, protein C levels were significantly lower (p = 0.007) and PAI-1 levels were higher (p = 0.026) in subjects with PGD than in others. These differences persisted despite adjustment for potential confounders in multivariate analyses. Higher recipient pulmonary artery pressures, measured immediately pretransplantation, were associated with higher PAI-1 levels and increased risk of PGD.
Lower postoperative protein C and higher PAI-1 plasma levels are associated with PGD after lung transplantation. Impaired fibrinolysis and enhanced coagulation may be important in PGD pathogenesis.
急性肺损伤的特征为高凝状态和纤溶功能受损。我们推测，血浆中蛋白C水平降低和1型纤溶酶原激活物抑制剂（PAI-1）水平升高与肺移植后的原发性移植肺功能障碍（PGD）相关。
前瞻性多中心队列研究。
我们在六个中心对128例肺移植受者在肺移植前以及同种异体肺再灌注后6、24、48和72小时测量了血浆蛋白C和PAI-1水平。主要结局为移植后72小时的3级PGD（Pa(O₂)/Fi(O₂) < 200且伴有肺泡浸润）。使用逻辑回归和广义估计方程评估生物标志物谱。
发生PGD的患者移植后24小时的蛋白C水平低于未发生PGD的患者（均值±标准差[相对于对照组]：分别为64±27%和92±41%；p = 0.002）。发生PGD的患者在24小时时的PAI-1水平几乎是未发生PGD患者的两倍（分别为213±144和117±89 ng/ml；p < 0.001）。在术后72小时内，发生PGD的受试者的蛋白C水平显著较低（p = 0.007），PAI-1水平较高（p = 0.026）。尽管在多变量分析中对潜在混杂因素进行了校正，但这些差异仍然存在。移植前即刻测量的较高受者肺动脉压与较高的PAI-1水平及PGD风险增加相关。
肺移植后较低的术后蛋白C水平和较高的PAI-1血浆水平与PGD相关。纤溶功能受损和凝血增强可能在PGD发病机制中起重要作用。
