保留血胸(RH)是胸膜内出血的常见且潜在的严重并发症,可导致肺限制。提倡早期手术干预和胸膜内纤溶疗法。然而,缺乏可靠的,适合介入检测的成本效益模型阻碍了我们对药物干预在RH管理中的作用的理解。这里,我们报道了一种新的兔RH模型的发展。RH是通过胸管依次施用多达三个剂量的再钙化的柠檬酸盐同源兔供体血加凝血酶来诱导的。诱导后4、7和10天的RH(分别为RH4,RH7和RH10)以凝块保留为特征,胸膜内组织,胸膜皮增加,与临床RH相似。超声和计算机断层扫描(CT)等临床成像技术揭示了胸膜内凝块随时间的动态形成和吸收以及由此产生的肺限制。在两种性别的年轻(3个月)动物中评估了RH7和RH10。RH7概述了临床上最相关的RH属性;因此,我们进一步使用该模型来评估年龄对RH发育的影响.模型中的血液胸腔液(PF)通常很小,并且在不同模型中检测到可变。兔模型PFs表现出促炎反应,使人联想到人血胸PFs。总的来说,RH7导致持久的胸膜内凝块的一致形成,胸膜粘连,胸膜增厚,和肺限制。实现了7d以上的长期胸管放置,能够直接进入胸膜内进行采样和治疗。模型,特别是RH7,适合测试新的胸膜腔内药物干预措施,包括当前使用的经验剂量的药物或旨在安全和更有效地清除RH的新候选药物的迭代。
Retained hemothorax (RH) is a commonly encountered and potentially severe complication of intrapleural bleeding that can organize with lung restriction. Early surgical intervention and intrapleural fibrinolytic therapy have been advocated. However, the lack of a reliable, cost-effective model amenable to interventional testing has hampered our understanding of the role of pharmacological interventions in RH management. Here, we report the development of a new RH model in rabbits. RH was induced by sequential administration of up to three doses of recalcified citrated homologous rabbit donor blood plus thrombin via a chest tube. RH at 4, 7, and 10 days post-induction (RH4, RH7, and RH10, respectively) was characterized by clot retention, intrapleural organization, and increased pleural rind, similar to that of clinical RH. Clinical imaging techniques such as ultrasonography and computed tomography (CT) revealed the dynamic formation and resorption of intrapleural clots over time and the resulting lung restriction. RH7 and RH10 were evaluated in young (3 mo) animals of both sexes. The RH7 recapitulated the most clinically relevant RH attributes; therefore, we used this model further to evaluate the effect of age on RH development. Sanguineous pleural fluids (PFs) in the model were generally small and variably detected among different models. The rabbit model PFs exhibited a proinflammatory response reminiscent of human hemothorax PFs. Overall, RH7 results in the consistent formation of durable intrapleural clots, pleural adhesions, pleural thickening, and lung restriction. Protracted chest tube placement over 7 d was achieved, enabling direct intrapleural access for sampling and treatment. The model, particularly RH7, is amenable to testing new intrapleural pharmacologic interventions, including iterations of currently used empirically dosed agents or new candidates designed to safely and more effectively clear RH.