A Novel Rabbit Model of Retained Hemothorax with Pleural Organization.

A Novel Rabbit Model of Retained Hemothorax with Pleural Organization.
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一种新型的兔子模型,保留了胸膜组织。

DOI:
10.3390/ijms25010470
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发表时间:
2023-12-29
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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滞留血胸 (RH) 是一种常见且可能严重的胸膜内出血并发症,可导致肺部受限。提倡早期手术干预和胸膜腔内纤溶治疗。然而,缺乏适合介入测试的可靠、具有成本效益的模型阻碍了我们对药物干预在 RH 管理中作用的理解。在这里,我们报告了一种新的兔子 RH 模型的开发。通过胸管连续给予最多三剂再钙化的柠檬酸同源兔供体血液加凝血酶来诱导 RH。诱导后 4、7 和 10 天的 RH(分别为 RH4、RH7 和 RH10)的特点是凝块滞留、胸膜内组织和胸膜增大,与临床 RH 相似。超声检查和计算机断层扫描 (CT) 等临床成像技术揭示了胸膜内血栓随时间的动态形成和吸收以及由此产生的肺部限制。在年轻(3 个月)的两性动物中评估 RH7 和 RH10。 RH7 概括了临床上最相关的 RH 属性;因此,我们进一步利用该模型来评估年龄对 RH 发育的影响。模型中的血性胸腔积液(PF)通常较小,并且在不同模型中检测到的情况不同。兔模型 PF 表现出促炎反应,类似于人类血胸 PF。总体而言,RH7 导致持久胸膜内血栓、胸膜粘连、胸膜增厚和肺限制的持续形成。实现了超过 7 天的长时间胸管放置,从而能够直接进入胸膜内进行采样和治疗。该模型,特别是 RH7,适合测试新的胸膜内药物干预措施,包括迭代当前使用的经验剂量药物或旨在安全、更有效地清除 RH 的新候选药物。
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.
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