Lawendy Abdel-Rahman, Bihari Aurelia, Sanders David W, Potter Richard F, Cepinskas Gediminas
*Division of Orthopaedic Surgery, University of Western Ontario, London, Ontario, Canada; †Centre for Critical Illness Research, Lawson Health Research Institute, London, Ontario, Canada; and ‡Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
J Orthop Trauma. 2014 Nov;28(11):e263-8. doi: 10.1097/BOT.0000000000000097.
To examine the protective effects of carbon monoxide (CO), liberated from a novel CO-releasing molecule (CORM-3), on the function of compartment syndrome (CS)-challenged muscle in a rodent model, thus providing for a potential development of a pharmacologic adjunctive treatment for CS.
Wistar rats were randomized into 4 groups: sham (no CS), CS, CS with inactive CORM-3 (iCORM-3), and CS + CORM-3 (10 mg/kg intraperitoneally). CS was induced by elevation of intracompartmental pressure to 30 mm Hg through an infusion of isotonic saline into the anterior compartment of the hind limb for 2 hours. Both CORM-3 and iCORM-3 were injected immediately after fasciotomy. Microvascular perfusion, cellular tissue injury, and inflammatory response within the extensor digitorum longus muscle were assessed using intravital video microscopy 45 minutes after fasciotomy. Systemic levels of tumor necrosis factor alpha (TNF-α) were also measured.
Elevation of intracompartmental pressure resulted in significant microvascular perfusion deficits (23% ± 2% continuously perfused capillaries in CS vs. 76% ± 4% in sham, P < 0.0001; 55% ± 2% nonperfused capillaries in CS vs. 13% ± 2% in sham, P < 0.0001), significant increase in tissue injury (ethidium bromide/bisbenzimide of 0.31 ± 0.05 in CS vs. 0.05 ± 0.03 in sham, P < 0.0001) and adherent leukocytes (13.7 ± 0.9 in CS vs. 1.8 ± 0.5 in sham, P < 0.0001), and a progressive rise in systemic TNF-α. CORM-3 (but not iCORM-3) treatment restored the number of continuously perfused capillaries (57% ± 5%, P < 0.001), diminished tissue injury (ethidium bromide/bisbenzimide of 0.07 ± 0.01, P < 0.001), reversed the CS-associated rise in TNF-α, and decreased leukocyte adherence (0.6 ± 0.3, P < 0.001).
CORM-3 displays a potent protective/anti-inflammatory action in an experimental model of CS, suggesting a potential therapeutic application to patients at risk of developing CS.
研究一种新型一氧化碳释放分子（CORM-3）释放的一氧化碳（CO）对啮齿动物模型中骨筋膜室综合征（CS）损伤肌肉功能的保护作用，从而为CS的药物辅助治疗提供潜在的发展方向。
将Wistar大鼠随机分为4组：假手术组（无CS）、CS组、CS+无活性CORM-3（iCORM-3）组和CS+CORM-3组（腹腔注射10mg/kg）。通过向后肢前侧骨筋膜室内输注等渗盐水2小时，使骨筋膜室内压力升高至30mmHg来诱导CS。在筋膜切开术后立即注射CORM-3和iCORM-3。在筋膜切开术后45分钟，使用活体视频显微镜评估趾长伸肌内的微血管灌注、细胞组织损伤和炎症反应。还测量了全身肿瘤坏死因子α（TNF-α）水平。
骨筋膜室内压力升高导致微血管灌注显著不足（CS组持续灌注的毛细血管为23%±2%，假手术组为76%±4%，P<0.0001；CS组无灌注的毛细血管为55%±2%，假手术组为13%±2%，P<0.0001），组织损伤显著增加（CS组溴化乙锭/双苯甲酰亚胺为0.31±0.05，假手术组为0.05±0.03，P<0.0001），黏附白细胞增多（CS组为13.7±0.9，假手术组为1.8±0.5，P<0.0001），全身TNF-α逐渐升高。CORM-3（而非iCORM-3）治疗可恢复持续灌注的毛细血管数量（57%±5%，P<0.001），减轻组织损伤（溴化乙锭/双苯甲酰亚胺为0.07±0.01，P<0.001），逆转CS相关的TNF-α升高，并减少白细胞黏附（0.6±0.3，P<0.001）。
CORM-3在CS实验模型中显示出强大的保护/抗炎作用，提示其对有发生CS风险的患者具有潜在的治疗应用价值。
