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严重热烧伤后用腺嘌呤、利多卡因和镁(ALM)复苏的肺保护作用及在大鼠模型中假手术的重要性。

Lung Protection After Severe Thermal Burns With Adenosine, Lidocaine, and Magnesium (ALM) Resuscitation and Importance of Shams in a Rat Model.

机构信息

Heart and Trauma Research Laboratory, College of Medicine and Dentistry, James Cook University, Queensland 4811, Australia.

出版信息

J Burn Care Res. 2024 Jan 5;45(1):216-226. doi: 10.1093/jbcr/irad127.

Abstract

The management of severe burns remains a complex challenge. Adenosine, lidocaine, and magnesium (ALM) resuscitation therapy has been shown to protect against hemorrhagic shock and traumatic injury. The aim of the present study was to investigate the early protective effects of small-volume ALM fluid resuscitation in a rat model of 30% total body surface area (TBSA) thermal injury. Male Sprague-Dawley rats (320-340 g; n = 25) were randomly assigned to: 1) Sham (surgical instrumentation and saline infusion, without burn, n = 5), 2) Saline resuscitation group (n = 10), or 3) ALM resuscitation group (n = 10). Treatments were initiated 15-min after burn trauma, including 0.7 mL/kg 3% NaCl ± ALM bolus and 0.25-0.5 mL/kg/h 0.9% NaCl ± ALM drip, with animals monitored to 8.25-hr post-burn. Hemodynamics, cardiac function, blood chemistry, hematology, endothelial injury markers and histopathology were assessed. Survival was 100% for Shams and 90% for both ALM and Saline groups. Shams underwent significant physiological, immune and hematological changes over time as a result of surgical traums. ALM significantly reduced malondialdehyde levels in the lungs compared to Saline (P = .023), and showed minimal alveolar destruction and inflammatory cell infiltration (P < .001). ALM also improved cardiac function and oxygen delivery (21%, P = .418 vs Saline), reduced gut injury (P < .001 vs Saline), and increased plasma adiponectin (P < .001 vs baseline). Circulating levels of the acute phase protein alpha 1-acid glycoprotein (AGP) increased 1.6-times (P < .001), which may have impacted ALM's therapeutic efficacy. We conclude that small-volume ALM therapy significantly reduced lung oxidative stress and preserved alveolar integrity following severe burn trauma. Further studies are required to assess higher ALM doses with longer monitoring periods.

摘要

严重烧伤的治疗仍然是一个复杂的挑战。腺苷、利多卡因和镁(ALM)复苏疗法已被证明可预防出血性休克和创伤性损伤。本研究的目的是探讨小容量 ALM 液复苏在 30%总体表面积(TBSA)热烧伤大鼠模型中的早期保护作用。雄性 Sprague-Dawley 大鼠(320-340g;n=25)随机分为:1)假手术组(手术器械和生理盐水输注,无烧伤,n=5),2)生理盐水复苏组(n=10),或 3)ALM 复苏组(n=10)。治疗于烧伤后 15 分钟开始,包括 0.7ml/kg 3%NaCl±ALM 弹丸和 0.25-0.5ml/kg/h 0.9%NaCl±ALM 滴注,动物监测至烧伤后 8.25 小时。评估血流动力学、心功能、血液化学、血液学、内皮损伤标志物和组织病理学。假手术组和 ALM 组及生理盐水组的存活率均为 100%。假手术组由于手术创伤,随着时间的推移经历了显著的生理、免疫和血液学变化。与生理盐水组相比,ALM 显著降低了肺组织中的丙二醛水平(P=0.023),且表现出最小的肺泡破坏和炎症细胞浸润(P<0.001)。ALM 还改善了心功能和氧输送(21%,P=0.418 与生理盐水相比),减少了肠道损伤(P<0.001 与生理盐水相比),并增加了血浆脂联素(P<0.001 与基线相比)。循环中的急性期蛋白α 1-酸性糖蛋白(AGP)增加了 1.6 倍(P<0.001),这可能影响了 ALM 的治疗效果。我们的结论是,小容量 ALM 治疗可显著减轻严重烧伤后肺组织的氧化应激,保持肺泡完整性。需要进一步研究评估更高剂量的 ALM 和更长的监测期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab96/10768784/d59873b36976/irad127_fig1.jpg

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