Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital, Ulm, Germany.
Department of Anesthesiology, University Hospital, Ulm, Germany.
Shock. 2019 Jan;51(1):68-77. doi: 10.1097/SHK.0000000000001115.
Hemorrhagic shock accounts for a large amount of trauma-related mortality. The severity of trauma can be further aggravated by an additional blunt chest trauma (TxT), which independently contributes to mortality upon the development of an acute lung injury (ALI). Besides, cigarette smoke (CS) exposure before TxT enhanced posttraumatic inflammation, thereby aggravating ALI. We therefore aimed to characterize the impact of an acute and/or chronic lung injury on organ dysfunction in a murine model of traumatic hemorrhagic shock (HS).
After 3 weeks of CS exposure, anesthetized mice underwent HS with/without TxT. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain mean arterial pressure ≥50 mmHg. Lung mechanics and gas exchange were assessed together with systemic hemodynamics, metabolism, and acid-base status. Postmortem blood and tissue samples were analyzed for cytokine and chemokine levels, protein expression, mitochondrial respiration, and histological changes.
CS exposure and HS alone coincided with increased inflammation, decreased whole blood sulfide concentrations, and decreased diaphragmatic mitochondrial respiration. CS-exposed mice, which were subjected to TxT and subsequent HS, showed hemodynamic instability, acute kidney injury, and high mortality.
Chronic CS exposure per se had the strongest impact on inflammatory responses. The degree of inflammation was similar upon an additional TxT, however, mice presented with organ dysfunction and increased mortality rates. Hence, in mice the degree of inflammation may be dissociated from the severity of organ dysfunction or injury.
失血性休克导致了大量创伤相关死亡。钝性胸部创伤（TxT）的进一步加重会使创伤严重程度进一步恶化，并且在发生急性肺损伤（ALI）时独立导致死亡率升高。此外，TxT 前暴露于香烟烟雾（CS）会增强创伤后的炎症，从而加重 ALI。因此，我们旨在描述在创伤性失血性休克（HS）的小鼠模型中急性和/或慢性肺损伤对器官功能障碍的影响。
在 CS 暴露 3 周后，麻醉小鼠进行 HS 合并/不合并 TxT。失血性休克持续 1 小时，然后输回失血并进行 4 小时的强化护理治疗，包括肺保护性机械通气、液体复苏以及去甲肾上腺素滴定以维持平均动脉压≥50mmHg。评估肺力学和气体交换与全身血流动力学、代谢和酸碱状态一起进行。对死后血液和组织样本进行细胞因子和趋化因子水平、蛋白表达、线粒体呼吸和组织学变化分析。
CS 暴露和单独的 HS 均导致炎症增加、全血硫化物浓度降低和膈肌线粒体呼吸降低。接受 TxT 和随后的 HS 的 CS 暴露小鼠表现出血流动力学不稳定、急性肾损伤和高死亡率。
慢性 CS 暴露本身对炎症反应的影响最大。另外的 TxT 导致的炎症程度相似，但小鼠出现了器官功能障碍和更高的死亡率。因此，在小鼠中，炎症的程度可能与器官功能障碍或损伤的严重程度脱钩。
