Chen L E, Seaber A V, Nasser R M, Stamler J S, Urbaniak J R
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Physiol. 1998 Mar;274(3):R822-9. doi: 10.1152/ajpregu.1998.274.3.R822.
The ultimate goal of replantation and microsurgical reconstructive operations is to regain or improve impaired function of the tissue. However, the data related to the influence of NO on tissue function are limited. This study evaluated the effects of the NO donor S-nitroso-N-acetylcysteine (SNAC) on contractile function of skeletal muscle during reperfusion. Forty-nine rats were divided into six groups. The extensor digitorum longus (EDL) muscles in groups I and II were not subjected to ischemia-reperfusion but were treated with a low (100 nmol/min) or high (1 mumol/min) dose of SNAC. In groups III-V, the EDL underwent 3 h of ischemia and 3 h of reperfusion and was also treated with low (100 nmol/min) or high doses (1 or 5 mumol/min) of SNAC. Group VI was a phosphate-buffered saline (PBS)-treated control group. Twenty additional animals were used to document systemic effects of SNAC and PBS only. SNAC or PBS was infused for 6.5 h, beginning 30 min before ischemia and continuing throughout the duration of reperfusion. Contractile testing compared the maximal twitch force, isometric tetanic contractile forces, fatigue, and fatigue half time of the experimental EDL and the contralateral nontreated EDL. The findings indicate that 1) SNAC does not influence contractile function of EDL muscle not subjected to ischemia-reperfusion, 2) SNAC significantly protects the contractile function of ischemic skeletal muscle against reperfusion injury in the early reperfusion period, and 3) the protective role of SNAC is critically dosage dependent; protection is lost at higher doses. The conclusion from this study is that supplementation with exogenous NO exerts a protective effect on the tissue against reperfusion injury.
再植和显微外科重建手术的最终目标是恢复或改善受损组织的功能。然而,关于一氧化氮(NO)对组织功能影响的数据有限。本研究评估了NO供体S-亚硝基-N-乙酰半胱氨酸(SNAC)在再灌注期间对骨骼肌收缩功能的影响。49只大鼠被分为六组。第一组和第二组的趾长伸肌(EDL)未经历缺血再灌注,但分别用低剂量(100 nmol/min)或高剂量(1 μmol/min)的SNAC处理。第三组至第五组的EDL经历3小时缺血和3小时再灌注,同样分别用低剂量(100 nmol/min)或高剂量(1或5 μmol/min)的SNAC处理。第六组是磷酸盐缓冲盐水(PBS)处理的对照组。另外使用20只动物仅记录SNAC和PBS的全身效应。在缺血前30分钟开始输注SNAC或PBS,持续6.5小时,贯穿再灌注全过程。收缩功能测试比较了实验侧EDL和对侧未处理EDL的最大抽搐力、等长强直收缩力、疲劳程度和疲劳半衰期。研究结果表明:1)SNAC不影响未经历缺血再灌注的EDL肌肉的收缩功能;2)在再灌注早期,SNAC能显著保护缺血骨骼肌的收缩功能免受再灌注损伤;3)SNAC的保护作用具有关键的剂量依赖性,高剂量时保护作用丧失。本研究的结论是,补充外源性NO对组织免受再灌注损伤具有保护作用。