Las Vegas, Nev. From the Department of Surgery, Division of Plastic Surgery, University of Nevada School of Medicine.
Plast Reconstr Surg. 2011 Oct;128(4):279e-287e. doi: 10.1097/PRS.0b013e3182268b9a.
Recently, nitrite has been rediscovered as a physiologically relevant storage reservoir of nitric oxide in blood and it can readily be converted to nitric oxide under hypoxic and acidic conditions. In this study, the authors evaluated the therapeutic efficacy of nitrite on reperfusion-induced microcirculatory alterations and mitochondrial dysfunction in the microvasculature of skeletal muscle.
The authors used a vascular pedicle isolated rat cremaster model that underwent 4 hours of warm ischemia followed by 2 hours or 17 hours of reperfusion. At 5 minutes before reperfusion, normal saline, sodium nitrite (0.20 μM/minute/kg), or nitrite mixed with 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (potassium salt) (0.2 mg/minute/kg) was infused into the microcirculation of ischemic cremaster by means of intraarterial infusion. Ischemia-reperfusion-induced microcirculatory alterations were measured after 2 hours of reperfusion. Microvasculature of the cremaster muscle including the vascular pedicle was harvested to determine the mitochondrial dysfunction. The blood concentration of methemoglobin was also measured to determine the toxicity of nitrite.
The authors found that nitrite significantly attenuated ischemia-reperfusion-induced vasoconstriction, arteriole stagnation, and capillary no-reflow in the early phase of reperfusion and the depolarization of mitochondrial membrane potential and cytochrome c release in the late phase of reperfusion. Nitrite-induced protection was significantly blocked by a nitric oxide scavenger (potassium salt). The methemoglobin results showed that the doses of nitrite we used in the present study were safe.
The supplementation of a low dose of nitrite, directly into the microcirculation of ischemic muscle through local intraarterial infusion, significantly attenuated ischemia-reperfusion-induced microcirculatory alterations in vivo and mitochondrial dysfunction in vitro in the microvasculature of skeletal muscle.
最近，亚硝酸盐作为血液中一氧化氮的一种生理相关储存库重新被发现，它可以在缺氧和酸性条件下很容易地转化为一氧化氮。在这项研究中，作者评估了亚硝酸盐对再灌注引起的骨骼肌微循环改变和线粒体功能障碍的治疗效果。
作者使用了一个血管蒂分离的大鼠提睾肌模型，该模型经历了 4 小时的热缺血，随后进行 2 小时或 17 小时的再灌注。在再灌注前 5 分钟，通过动脉内输注将生理盐水、亚硝酸钠（0.20 μM/分钟/公斤）或亚硝酸盐与 2-（4-羧基苯基）-4,5-二氢-4,4,5,5-四甲基咪唑啉-3-氧化物-1-氧（钾盐）（0.2 毫克/分钟/公斤）混合注入缺血性提睾肌的微循环中。在再灌注 2 小时后测量再灌注引起的微循环改变。收获提睾肌的微血管，包括血管蒂，以确定线粒体功能障碍。还测量了血液中亚铁血红蛋白的浓度以确定亚硝酸盐的毒性。
作者发现，亚硝酸盐显著减轻了再灌注早期的血管收缩、小动脉停滞和毛细血管无复流，以及再灌注晚期的线粒体膜电位去极化和细胞色素 c 释放。一氧化氮清除剂（钾盐）显著阻断了亚硝酸盐诱导的保护作用。高铁血红蛋白的结果表明，我们在本研究中使用的亚硝酸盐剂量是安全的。
通过局部动脉内输注将低剂量的亚硝酸盐直接补充到缺血肌肉的微循环中，显著减轻了骨骼肌微血管再灌注引起的体内微循环改变和体外线粒体功能障碍。
