The time course of resolution of adhesions during fibrinolytic therapy in tetracycline-induced pleural injury in rabbits.
The time course of resolution of adhesions during fibrinolytic therapy in tetracycline-induced pleural injury in rabbits.
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兔四环素引起的胸膜损伤纤溶治疗期间粘连消退的时间过程。
DOI：
10.1152/ajplung.00136.2015
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Idell,Steven
中科院分区：
文献类型：
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作者：
Komissarov,AndreyA;Florova,Galina;Azghani,AliO;Buchanan,Ann;Bradley,WilliamM;Schaefer,Chris;Koenig,Kathleen;Idell,Steven
胸膜内纤溶治疗（IPFT）后有效清除胸膜粘连/组织所需的时间尚不清楚。采用胸部超声检查和计算机断层扫描 (CT) 来评估 IPFT 在四环素诱导的胸膜损伤兔模型中的疗效，并用单链 (sc) 尿激酶纤溶酶原激活剂 (scuPA) 或组织 PA (sctPA) 治疗。使用 sctPA (0.145 mg/kg;n= 10) 和 scuPA (0.5 mg/kg;n= 12) 的 IPFT 单独通过连续超声检查 (n= 12) 或与 CT 扫描 (n= 10) 一起监测。 IPFT 疗效通过大体肺损伤评分 (GLIS) 和超声检查评分 (USS) 进行评估。 IPFT 后 0-240 分钟和 24 小时抽取的胸腔积液进行 PA 和纤溶活性、α-巨球蛋白/纤溶素复合物和活性 PA 抑制剂 1 (PAI-1) 的检测。 scuPA 和 sctPA 在 20 分钟内产生了相当的稳态纤溶活性。 scuPA 组的 PA 活性下降速度慢于 sctPA 组（kobs= 0.016 和 0.042 min−1）。 IPFT 后 0-40 分钟积累了大量生物活性 uPA/α-巨球蛋白（但不是 tPA；P< 0.05）复合物。尽管胸腔内处理存在差异，但使用任一纤溶素进行 IPFT 对仅通过超声检查成像的动物都是有效的 (GLIS ≤ 10)。 USS 与死后 GLIS 相关性良好（r2 = 0.85），并证实 IPFT 后胸膜内纤维蛋白溶解相对缓慢，这与 4-8 小时粘连/组织的有效清除相一致。 CT 扫描与治疗后 24 小时 IPFT 效果较差（GLIS > 10）和较高水平的活性 PAI-1 相关。我们得出的结论是，四环素引起的家兔胸膜损伤中胸膜内纤维蛋白溶解相对缓慢（4-8小时）。在 CT 扫描动物中，PAI-1 活性升高（可能是辐射引起的）会降低 IPFT 的功效，从而增强了活性 PAI-1 对 IPFT 结果的主要影响。
The time required for the effective clearance of pleural adhesions/organization after intrapleural fibrinolytic therapy (IPFT) is unknown. Chest ultrasonography and computed tomography (CT) were used to assess the efficacy of IPFT in a rabbit model of tetracycline-induced pleural injury, treated with single-chain (sc) urokinase plasminogen activators (scuPAs) or tissue PAs (sctPA). IPFT with sctPA (0.145 mg/kg;n= 10) and scuPA (0.5 mg/kg;n= 12) was monitored by serial ultrasonography alone (n= 12) or alongside CT scanning (n= 10). IPFT efficacy was assessed with gross lung injury scores (GLIS) and ultrasonography scores (USS). Pleural fluids withdrawn at 0–240 min and 24 h after IPFT were assayed for PA and fibrinolytic activities, α-macroglobulin/fibrinolysin complexes, and active PA inhibitor 1 (PAI-1). scuPA and sctPA generated comparable steady-state fibrinolytic activities by 20 min. PA activity in the scuPA group decreased slower than the sctPA group (kobs= 0.016 and 0.042 min−1). Significant amounts of bioactive uPA/α-macroglobulin (but not tPA;P< 0.05) complexes accumulated at 0–40 min after IPFT. Despite the differences in intrapleural processing, IPFT with either fibrinolysin was effective (GLIS ≤ 10) in animals imaged with ultrasonography only. USS correlated well with postmortem GLIS (r2= 0.85) and confirmed relatively slow intrapleural fibrinolysis after IPFT, which coincided with effective clearance of adhesions/organization at 4–8 h. CT scanning was associated with less effective (GLIS > 10) IPFT and higher levels of active PAI-1 at 24 h following therapy. We concluded that intrapleural fibrinolysis in tetracycline-induced pleural injury in rabbits is relatively slow (4–8 h). In CT-scanned animals, elevated PAI-1 activity (possibly radiation induced) reduced the efficacy of IPFT, buttressing the major impact of active PAI-1 on IPFT outcomes.