Strange C, Baumann M H, Sahn S A, Idell S
Department of Medicine, Medical University of South Carolina, Charleston 29425.
Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):508-15. doi: 10.1164/ajrccm.151.2.7842213.
Extravascular fibrin deposition is common at sites of pleural injury and has been related to loculation of pleural fluids. Although thrombolytic therapy has been used to treat pleural loculations, it has not been compared with pleural administration of anticoagulant therapy. We therefore tested interventional strategies designed to compare the relative effects of in vivo anticoagulation or supplemented fibrinolysis on pleural injury, and to characterize the local tissue responses to these modalities. Early intrapleural instillation of saline (Group 1), heparin 1,000 IU (Group 2), or urokinase (uPA) 1,500 IU (Group 3) every 12 h for 3 d was used to interrupt pleural adhesion formation and pleural fibrosis induced by tetracycline hydrochloride in rabbits. Procoagulant and fibrinolytic activities were determined in pleural effusion samples obtained serially every 12 h after the last administered intrapleural dose. Pleural fluid procoagulant activity was blocked by intrapleural heparin (p < 0.001), but plasminogen-dependent fibrinolytic activity was rarely increased by intrapleural urokinase. Most plasminogen activator activity in the pleural fluids was found at high-molecular-weight regions by enzymography, suggesting that it was bound to inhibitor(s). Pathologic analysis at 14 d demonstrated that the number of pleural adhesions in the heparin (8.4 +/- 3.4, mean +/- standard error) and uPA groups (6.1 +/- 2.5) was less than in saline-treated tetracycline controls (20.7 +/- 4.7) (both p < 0.02). Visceral pleural thickness did not differ between groups (p = NS). We conclude that intrapleural heparin or uPA are equally effective in decreasing intrapleural adhesions in tetracycline-induced pleural injury. The data indicate that early anticoagulation or fibrinolytic intervention can attenuate subsequent pleural symphysis in this model.
血管外纤维蛋白沉积在胸膜损伤部位很常见，并且与胸腔积液的包裹形成有关。尽管溶栓疗法已被用于治疗胸腔积液包裹，但尚未与胸膜内给予抗凝治疗进行比较。因此，我们测试了一些介入策略，旨在比较体内抗凝或补充纤溶对胸膜损伤的相对影响，并描述局部组织对这些治疗方式的反应。通过每12小时向兔胸腔内早期滴注生理盐水（第1组）、1000 IU肝素（第2组）或1500 IU尿激酶（uPA）（第3组），持续3天，以阻断盐酸四环素诱导的胸膜粘连形成和胸膜纤维化。在最后一次胸腔内给药后，每12小时连续采集胸腔积液样本，测定其促凝和纤溶活性。胸腔内肝素可阻断胸腔积液的促凝活性（p < 0.001），但胸腔内尿激酶很少能增加纤溶酶原依赖性纤溶活性。通过酶谱分析发现，胸腔积液中的大多数纤溶酶原激活剂活性位于高分子量区域，提示其与抑制剂结合。14天时的病理分析表明，肝素组（8.4±3.4，平均值±标准误）和uPA组（6.1±2.5）的胸膜粘连数量少于生理盐水处理的四环素对照组（20.7±4.7）（p均< 0.02）。各组间脏层胸膜厚度无差异（p = 无显著性差异）。我们得出结论，胸腔内肝素或uPA在减少四环素诱导的胸膜损伤中的胸腔内粘连方面同样有效。数据表明，在该模型中早期抗凝或纤溶干预可减轻随后的胸膜粘连。
