Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction
Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction
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DOI：
10.1161/circulationaha.107.748814
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发表时间：
2008-06-10
期刊：
影响因子：
37.8
通讯作者：
Arai, Andrew E.
中科院分区：
文献类型：
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作者：
Gonzalez, Felix M.;Shiva, Sruti;Arai, Andrew E.
背景-越来越多的证据表明，普遍存在的阴离子亚硝酸盐(NO2-)是一种生理信号分子，在血管内分泌一氧化氮运输、缺氧血管扩张、信号传递和细胞保护中发挥作用。因此，亚硝酸盐可提高急性心肌梗死再灌注治疗的疗效。本研究的具体目的是(1)评估亚硝酸盐在减少犬心肌梗死坏死和凋亡中的作用；(2)确定亚硝酸盐与化学中间体(如S-亚硝硫醇)的相对作用。方法和结果-我们通过组织病理学、微球和磁共振成像对27只犬冠状动脉闭塞120分钟后的心肌梗死范围、微血管灌注量和左心功能进行了评估。这是一项盲法前瞻性研究，将生理盐水对照组(n=9)与缺血最后60分钟(n=9)和最后5分钟(n=9)静脉注射亚硝酸盐进行比较。在盐水处理的对照组动物中，70%+/-10%的危险区域发生了脑梗塞，相比之下，接受60分钟亚硝酸盐输注的动物的这一比例为23%+/-5%。值得注意的是，在缺血的最后5分钟内输注亚硝酸盐也限制了梗塞的范围(危险区域的36+/-8%)。亚硝酸盐改善微血管灌流，减少细胞凋亡，改善收缩功能。在5min的亚硝酸盐输注过程中，S亚硝硫醇和亚硝酸铁蛋白加合物均未积聚，提示亚硝酸根是具有心脏保护作用的血管内一氧化氮活性物种。结论亚硝酸根作为急性心肌梗死再灌注治疗的辅助治疗手段，具有显著的应用潜力。
Background - Accumulating evidence suggests that the ubiquitous anion nitrite (NO2-) is a physiological signaling molecule, with roles in intravascular endocrine nitric oxide transport, hypoxic vasodilation, signaling, and cytoprotection. Thus, nitrite could enhance the efficacy of reperfusion therapy for acute myocardial infarction. The specific aims of this study were (1) to assess the efficacy of nitrite in reducing necrosis and apoptosis in canine myocardial infarction and (2) to determine the relative role of nitrite versus chemical intermediates, such as S-nitrosothiols.Methods and Results - We evaluated infarct size, microvascular perfusion, and left ventricular function by histopathology, microspheres, and magnetic resonance imaging in 27 canines subjected to 120 minutes of coronary artery occlusion. This was a blinded, prospective study comparing a saline control group (n = 9) with intravenous nitrite during the last 60 minutes of ischemia (n = 9) and during the last 5 minutes of ischemia (n = 9). In saline-treated control animals, 70 +/- 10% of the area at risk was infarcted compared with 23 +/- 5% in animals treated with a 60-minute nitrite infusion. Remarkably, a nitrite infusion in the last 5 minutes of ischemia also limited the extent of infarction (36 +/- 8% of area at risk). Nitrite improved microvascular perfusion, reduced apoptosis, and improved contractile function. S-Nitrosothiol and iron-nitrosyl-protein adducts did not accumulate in the 5-minute nitrite infusion, suggesting that nitrite is the bioactive intravascular nitric oxide species accounting for cardioprotection.Conclusions - Nitrite has significant potential as adjunctive therapy to enhance the efficacy of reperfusion therapy for acute myocardial infarction.