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腺苷、利多卡因和镁在猪模型中减轻主动脉复苏性血管内球囊阻断后再灌注损伤。

Adenosine, lidocaine, and magnesium for attenuating ischemia reperfusion injury from resuscitative endovascular balloon occlusion of the aorta in a porcine model.

机构信息

From the Department of Surgery (J.J.F., M.M.V., M.E.P., J.R.C., D.T.L., N.I., G.D.R., J.R.B.), Madigan Army Medical Center, Tacoma, Washington; and Department of Surgery (M.J.E.), University of North Carolina Medical Center, Chapel Hill, North Carolina.

出版信息

J Trauma Acute Care Surg. 2022 Apr 1;92(4):631-639. doi: 10.1097/TA.0000000000003482.

DOI:10.1097/TA.0000000000003482
PMID:34840271
Abstract

BACKGROUND

Minimally invasive resuscitative endovascular balloon occlusion of the aorta (REBOA) following noncompressible hemorrhage results in significant ischemia reperfusion injury (IRI). Adverse outcomes from IRI include organ dysfunction and can result in profound hemodynamic and molecular compromise. We hypothesized that adenosine, lidocaine, and magnesium (ALM) attenuates organ injury and inflammation responses following REBOA IRI in a porcine model of hemorrhage.

METHODS

Animals underwent a 20% controlled hemorrhage followed by 45 minutes of supraceliac balloon occlusion. They were randomized into two groups: control (n = 9) and ALM intervention (n = 9) to include a posthemorrhage, pre-REBOA bolus (200 mL of 3% NaCl ALM) followed by a continuous drip (2 mL/kg per hour of 0.9% NaCl ALM) during the 4-hour resuscitative period. Primary outcomes included hemodynamic parameters, gene expression of inflammatory signaling molecules, and plasma concentrations of select cytokines and chemokines.

RESULTS

The ALM cohort demonstrated a significant reduction in cardiac output and cardiac index. Plasma concentrations of interleukin 2 and interleukin 10 were significantly lower 3 hours post-REBOA in animals treated with ALM versus vehicle. Interleukin 4 levels in plasma were also lower with ALM at 3 and 4 hours post-REBOA (p < 0.05). Liver expression of IL1RN, MTOR, and LAMP3 messenger RNA was significantly lower with ALM as compared with the vehicle. No significant difference in large bowel gene expression was observed between treatments.

CONCLUSION

In a porcine model of hemorrhage, ALM treatment mitigated inflammatory responses early during post-REBOA resuscitation. Our findings suggest that ALM use with trauma may reduce inflammatory injury and improve outcomes related to REBOA utilization.

摘要

背景

非压迫性出血后行微创性主动脉球囊阻断复苏(REBOA)可导致明显的缺血再灌注损伤(IRI)。IRI 的不良后果包括器官功能障碍,并可导致严重的血液动力学和分子学障碍。我们假设腺苷、利多卡因和镁(ALM)可减轻猪模型出血后 REBOA IRI 后的器官损伤和炎症反应。

方法

动物经历 20%的控制性出血,随后进行 45 分钟的腹腔上动脉球囊阻断。将它们随机分为两组:对照组(n = 9)和 ALM 干预组(n = 9),包括出血后、REBOA 前(200 mL 3%NaCl-ALM )给予推注,随后在 4 小时复苏期间给予持续滴注(0.9%NaCl-ALM 2 mL/kg/h)。主要结局包括血流动力学参数、炎症信号分子的基因表达以及选择细胞因子和趋化因子的血浆浓度。

结果

ALM 组心输出量和心指数明显降低。与对照组相比,接受 ALM 治疗的动物在 REBOA 后 3 小时,白细胞介素 2 和白细胞介素 10 的血浆浓度显著降低。ALM 在 3 小时和 4 小时后,血浆中白细胞介素 4 水平也较低(p < 0.05)。与对照组相比,ALM 组肝 IL1RN、MTOR 和 LAMP3 信使 RNA 的表达明显降低。两种治疗方法之间,大肠基因表达无显著差异。

结论

在猪出血模型中,ALM 治疗可在 REBOA 复苏后早期减轻炎症反应。我们的研究结果表明,创伤时使用 ALM 可能会减轻炎症损伤,并改善与 REBOA 应用相关的结果。

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引用本文的文献

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Continuous renal replacement therapy with cytokine-adsorbing hemofilter to control resuscitative endovascular balloon occlusion of the aorta-related ischemia-reperfusion injury in a swine hemorrhagic shock model.在猪失血性休克模型中,采用细胞因子吸附血液滤过器进行持续肾脏替代疗法,以控制主动脉相关缺血再灌注损伤的复苏性血管内球囊阻断术。
Eur J Trauma Emerg Surg. 2025 Jan 24;51(1):66. doi: 10.1007/s00068-024-02707-4.
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Hydrogen gas inhalation therapy may not work sufficiently to mitigate oxidative stress induced with REBOA.
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Sci Rep. 2024 Dec 30;14(1):32128. doi: 10.1038/s41598-024-83934-y.
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Adenosine, lidocaine and Mg update: teaching old drugs new tricks.腺苷、利多卡因与镁的新进展:让老药发挥新作用
Front Med (Lausanne). 2023 Sep 27;10:1231759. doi: 10.3389/fmed.2023.1231759. eCollection 2023.