Apichartpiyakul Poon, Shinlapawittayatorn Krekwit, Rerkasem Kittipan, Chattipakorn Siriporn C, Chattipakorn Nipon
Department of Surgery, Vascular Surgery Unit, Clinical Surgical Research Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Department of Physiology, Cardiac Electrophysiology Unit, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
Ann Vasc Surg. 2022 Oct;86:452-481. doi: 10.1016/j.avsg.2022.04.040. Epub 2022 May 16.
This review aims to highlight mechanistic insights on skeletal muscle ischemia/reperfusion injury (IRI), a potentially life-threatening complication after acute lower limb ischemia. Lower limb IRI produces a wide spectrum of manifestations, ranging from local skeletal muscle necrosis to multi-organ failure. There is increasing evidence from both in vitro and in vivo reports to demonstrate several promising interventions that have successfully reduced IRI in skeletal muscle ischemic models. However, clinical studies to confirm their benefits are still lacking.
We conducted a comprehensive search of English literature listed in the PubMed database (All related published articles shown in PubMed until September 2020 have been included in this review), using the following keywords: acute limb ischemia, acute arterial occlusion, compartment syndrome, ischemic reperfusion injury, revascularization, and hypoxic reoxygenation.
A total of 58 articles pertinent to acute limb ischemia models were identified. The underlying mechanisms associated with IRI in skeletal muscle are due to excessive mitochondrial production of reactive oxygen species (ROS), cellular apoptosis and activation of inflammatory cascades. Several therapeutic interventions including both pharmacological and nonpharmacological treatments have been investigated and some showed promising results. These interventions include anti-oxidation, anti-inflammation, anti-hypertension, controlled-reperfusion, and ischemic preconditioning. Further clinical studies are needed to warrant their use in a clinical setting for lower limb IRI treatment.
This review comprehensively summarizes the mechanisms underlying IRI in lower limb ischemia. The reports currently available regarding the potential therapeutic interventions against lower limb IRI from in vitro, in vivo and clinical studies are presented and discussed. These findings may provide mechanistic insights for devising the strategies to improve the clinical outcomes in IRI patients in the near future. Further clinical studies are needed to warrant their use in a clinical setting for lower limb IRI treatment.
本综述旨在强调对骨骼肌缺血/再灌注损伤（IRI）的机制性见解，这是急性下肢缺血后一种可能危及生命的并发症。下肢IRI会产生广泛的表现，从局部骨骼肌坏死到多器官功能衰竭。越来越多的体外和体内研究报告证据表明，有几种有前景的干预措施已成功减轻了骨骼肌缺血模型中的IRI。然而，仍缺乏证实其益处的临床研究。
我们使用以下关键词对PubMed数据库中列出的英文文献进行了全面检索（本综述纳入了截至2020年9月PubMed中显示的所有相关已发表文章）：急性肢体缺血、急性动脉闭塞、骨筋膜室综合征、缺血再灌注损伤、血管重建和缺氧复氧。
共鉴定出58篇与急性肢体缺血模型相关的文章。骨骼肌IRI的潜在机制是由于线粒体过量产生活性氧（ROS）、细胞凋亡以及炎症级联反应的激活。已经研究了几种治疗干预措施，包括药物治疗和非药物治疗，一些显示出有前景的结果。这些干预措施包括抗氧化、抗炎、抗高血压、控制性再灌注和缺血预处理。需要进一步的临床研究以确保它们可用于临床治疗下肢IRI。
本综述全面总结了下肢缺血中IRI的潜在机制。展示并讨论了目前来自体外、体内和临床研究的关于针对下肢IRI的潜在治疗干预措施的报告。这些发现可能为在不久的将来设计改善IRI患者临床结局的策略提供机制性见解。需要进一步的临床研究以确保它们可用于临床治疗下肢IRI。
