The Severity of Microvascular Dysfunction Due to Compartment Syndrome Is Diminished by the Systemic Application of CO-Releasing Molecule-3
The Severity of Microvascular Dysfunction Due to Compartment Syndrome Is Diminished by the Systemic Application of CO-Releasing Molecule-3
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全身应用 CO 释放分子 3 可减轻室综合征引起的微血管功能障碍的严重程度
DOI：
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
G. Cepinskas
中科院分区：
文献类型：
--
作者：
A. Lawendy;A. Bihari;D. Sanders;R. Potter;G. Cepinskas
目的：在啮齿类动物模型中，研究新型 CO 释放分子 (CORM-3) 释放的一氧化碳 (CO) 对隔室综合征 (CS) 肌肉功能的保护作用，从而为 CS 药物辅助治疗的潜在开发提供可能。方法：将 Wistar 大鼠随机分为 4 组：假手术组（无 CS）、CS 组、带有失活 CORM-3 的 CS（iCORM-3）组和 CS + CORM-3（腹膜内注射 10 mg/kg）。通过将等渗盐水输注到后肢的前室2小时，将室内压力升高至30mmHg来诱导CS。 CORM-3 和 iCORM-3 均在筋膜切开后立即注射。筋膜切开术后 45 分钟，使用活体视频显微镜评估微血管灌注、细胞组织损伤和趾长伸肌内的炎症反应。还测量了肿瘤坏死因子α（TNF-α）的全身水平。结果：室内压力升高导致显着的微血管灌注不足（CS 中 23% ± 2% 连续灌注毛细血管 vs. 假手术中 76% ± 4%，P < 0.0001；CS 中 55% ± 2% 未灌注毛细血管 vs. 假手术中 13% ± 2%，P < 0.0001），组织损伤显着增加（乙锭）溴化物/双苯甲酰亚胺在 CS 中为 0.31 ± 0.05，而假手术中为 0.05 ± 0.03，P < 0.0001）和贴壁白细胞（CS 中为 13.7 ± 0.9，假手术中为 1.8 ± 0.5，P < 0.0001），全身性 TNF-α 逐渐升高。 CORM-3（但不是 iCORM-3）治疗恢复了持续灌注的毛细血管数量（57% ± 5%，P < 0.001），减少了组织损伤（溴化乙锭/双苯甲亚胺为 0.07 ± 0.01，P < 0.001），逆转了 CS 相关的 TNF-α 升高，并降低了白细胞粘附性（0.6 ± 0.3，P < 0.001）。结论：CORM-3 在 CS 实验模型中显示出有效的保护/抗炎作用，表明对有发生 CS 风险的患者具有潜在的治疗应用。
Objectives: 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. Methods: 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-&agr;) were also measured. Results: 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-&agr;. 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-&agr;, and decreased leukocyte adherence (0.6 ± 0.3, P < 0.001). Conclusions: 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.
影响因子：
6
作者：
Nakao, A;Kimizuka, K;Murase, N
通讯作者：
Murase, N
DOI：
10.1152/ajpheart.00971.2003
发表时间：
2004-05-01
影响因子：
4.8
作者：
Guo, YR;Stein, AB;Bolli, R
通讯作者：
Bolli, R