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皮下抗炎治疗预防猪接触烧伤模型中烧伤进展。

Subcutaneous Anti-inflammatory Therapies to Prevent Burn Progression in a Swine Model of Contact Burn Injury.

机构信息

Combat Wound Care, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX 78234, USA.

Plakous Therapeutics LLC, Winston-Salem, NC 27103, USA.

出版信息

Mil Med. 2024 Jul 3;189(7-8):1423-1431. doi: 10.1093/milmed/usad476.

DOI:10.1093/milmed/usad476
PMID:38150385
Abstract

INTRODUCTION

If left untreated, burn injuries can deepen or progress in depth within the first 72 hours after injury as a result of increased wound inflammation, subsequently worsening healing outcomes. This can be especially detrimental to warfighters who are constrained to resource-limited environments with delayed evacuation times to higher roles of care and more effective treatment. Preventing this burn progression at the point of injury has the potential to improve healing outcomes but requires a field-deployable therapy and delivery system. Subcutaneous therapies known to treat inflammation delivered local to the wound site may prove to be one such avenue for success.

MATERIALS AND METHODS

Seven Yorkshire-cross swine received partial-thickness burn injuries using a previously established contact burn model. Each animal received one of the seven therapies: (1) saline, (2) heparin, (3) ibuprofen, (4) erythropoietin, (5) resolvin, (6) rapamycin, and (7) placental extract, all of which are either currently employed or are experimental in field use and indicated to treat inflammation. Treatments were delivered subcutaneously on the day of injury and 24 hours post-injury to simulate a prolonged field care scenario, before potential evacuation. Animals and wound development were observed for 28 days before euthanasia. Throughout the course of the study, wounds were observed macroscopically via non-invasive imaging. Histological analyses provided the critical metric of burn progression. Treatment success criteria were designated as the ability to prevent burn progression past 80% of the dermal depth in two of the three treated wounds, a clinically relevant metric of burn progression.

RESULTS

It was determined that the applied model successfully created reproducible partial-thickness burn injuries in this porcine study. No significant differences with regard to lateral wound size or the rate of lateral wound closure were observed in any treatments. Several treatments including resolvin, rapamycin, ibuprofen, and erythropoietin successfully reduced burn progression to less than 80% of the dermal depth in two of the three wounds, 24 hours after injury.

CONCLUSIONS

This report employs an established model of porcine contact burn injury in order to test the ability of local subcutaneous delivery of therapeutics to prevent burn progression at the point of injury, via what is believed to be the inhibition of inflammation. Several treatments successfully prevented burn progression to a full-thickness injury, potentially improving wound healing outcomes in a simulated battlefield scenario. Subcutaneously administered therapies combating burn-induced inflammation at the point of injury may serve as a field-deployable treatment modality to improve warfighter recovery and return to duty.

摘要

简介

如果不加以治疗,烧伤会在受伤后 72 小时内由于伤口炎症加剧而加深或进一步恶化,从而导致愈合效果恶化。这对于被困在资源有限的环境中,撤离时间延迟,需要接受更高层次的治疗的战斗人员来说尤其不利。在受伤时预防这种烧伤进展有改善愈合效果的潜力,但需要一种可在现场部署的治疗和输送系统。局部给予已知可治疗炎症的皮下治疗可能是成功的途径之一。

材料和方法

七头约克郡杂交猪通过先前建立的接触烧伤模型接受部分厚度烧伤。每只动物接受七种治疗方法之一:(1)生理盐水,(2)肝素,(3)布洛芬,(4)促红细胞生成素,(5)分解素,(6)雷帕霉素和(7)胎盘提取物,所有这些都已被用于现场或正在现场使用的实验中,表明可治疗炎症。在潜在撤离前,在受伤当天和受伤后 24 小时将治疗药物皮下给药,以模拟长时间的现场护理场景。对动物和伤口发展进行了 28 天的观察,然后进行安乐死。在整个研究过程中,通过非侵入性成像观察伤口的宏观变化。组织学分析提供了烧伤进展的关键指标。治疗成功的标准被指定为在两个治疗伤口中的两个伤口中阻止烧伤进展超过真皮深度的 80%,这是烧伤进展的一个临床相关指标。

结果

该研究确定,所应用的模型在这项猪研究中成功地创建了可重复的部分厚度烧伤。在任何治疗中,侧面伤口大小或侧面伤口闭合率均无明显差异。几种治疗方法,包括分解素、雷帕霉素、布洛芬和促红细胞生成素,在受伤后 24 小时内成功地将烧伤进展减少到真皮深度的 80%以下。

结论

本报告采用了一种已建立的猪接触烧伤模型,以测试局部皮下给予治疗药物通过抑制炎症来防止受伤时烧伤进展的能力。几种治疗方法成功地阻止了烧伤进展到全层损伤,可能会改善模拟战场场景中的伤口愈合效果。在受伤时局部给予治疗烧伤引起的炎症的皮下治疗方法可能成为改善战斗人员康复和重返工作岗位的现场可部署治疗方式。

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