Department of Cellular and Molecular Biology, School of Medicine, The University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708, USA.
Department of Epidemiology and Biostatistics, School of Medicine, The University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708, USA.
Int J Mol Sci. 2024 Aug 12;25(16):8778. doi: 10.3390/ijms25168778.
Bleeding within the pleural space may result in persistent clot formation called retained hemothorax (RH). RH is prone to organization, which compromises effective drainage, leading to lung restriction and dyspnea. Intrapleural fibrinolytic therapy is used to clear the persistent organizing clot in lieu of surgery, but fibrinolysin selection, delivery strategies, and dosing have yet to be identified. We used a recently established rabbit model of RH to test whether intrapleural delivery of single-chain urokinase (scuPA) can most effectively clear RH. scuPA, or single-chain tissue plasminogen activator (sctPA), was delivered via thoracostomy tube on day 7 as either one or two doses 8 h apart. Pleural clot dissolution was assessed using transthoracic ultrasonography, chest computed tomography, two-dimensional and clot displacement measurements, and gross analysis. Two doses of scuPA (1 mg/kg) were more effective than a bolus dose of 2 mg/kg in resolving RH and facilitating drainage of pleural fluids (PF). Red blood cell counts in the PF of scuPA, or sctPA-treated rabbits were comparable, and no gross intrapleural hemorrhage was observed. Both fibrinolysins were equally effective in clearing clots and promoting pleural drainage. Biomarkers of inflammation and organization were likewise comparable in PF from both groups. The findings suggest that single-agent therapy may be effective in clearing RH; however, the clinical advantage of intrapleural scuPA remains to be established by future clinical trials.
胸腔内出血可能导致持续的血凝块形成，称为血胸残留（RH）。RH 容易发生组织化，这会影响有效引流，导致肺部受限和呼吸困难。胸腔内纤维蛋白溶解疗法用于清除持续存在的有组织的血凝块，而不是手术，但纤维蛋白溶解酶的选择、输送策略和剂量尚未确定。我们使用最近建立的 RH 兔模型来测试胸腔内单次链尿激酶（scuPA）给药是否可以最有效地清除 RH。scuPA 或单链组织型纤溶酶原激活剂（sctPA）在第 7 天通过胸腔引流管给药，每天 8 小时一次，或两次给药，间隔 8 小时。使用经胸超声、胸部计算机断层扫描、二维和血凝块移位测量以及大体分析评估胸腔内血凝块溶解情况。两剂 scuPA（1mg/kg）比 2mg/kg 的单次剂量更有效地解决 RH 并促进胸腔积液（PF）引流。scuPA 或 sctPA 治疗的兔子的 PF 中红细胞计数相当，并且没有明显的胸腔内出血。两种纤维蛋白溶解酶在清除血凝块和促进胸腔引流方面同样有效。PF 中的炎症和组织化生物标志物在两组中也相当。这些发现表明，单一药物治疗可能有效清除 RH；然而，胸腔内 scuPA 的临床优势仍有待未来的临床试验来确定。
