Biochemical signaling by remote ischemic conditioning of the arm versus thigh: Is one raise of the cuff enough?
Biochemical signaling by remote ischemic conditioning of the arm versus thigh: Is one raise of the cuff enough?
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DOI：
10.1016/j.redox.2017.03.010
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发表时间：
2017-08
期刊：
影响因子：
11.4
通讯作者：
Shiva S
中科院分区：
文献类型：
--
作者：
Dezfulian C;Taft M;Corey C;Hill G;Krehel N;Rittenberger JC;Guyette FX;Shiva S
远程缺血调节（RIC），由短暂的缺血和再灌注周期诱导，保护重要器官免受长时间的缺血损伤。虽然几种生化介质与RIC的作用机制有关，但RIC的定位或“剂量”是否影响保护性信号传导的程度仍不清楚。在这项健康个体的随机交叉研究中，我们测试了RIC的周期数及其定位（手臂与大腿）是否决定生化信号传导和细胞保护。受试者接受手臂或大腿RIC，然后在另一端接受RIC。在每个RIC周期后测量血流量、组织灌注、循环保护性介质亚硝酸盐浓度和血小板线粒体功能。我们发现血浆亚硝酸盐浓度在第一个RIC周期后达到峰值，并在整个RIC周期中保持升高。这种血浆亚硝酸盐在体外缺氧/再氧化心肌细胞模型中具有细胞保护作用。值得注意的是，尽管血浆亚硝酸盐在24小时恢复到基线水平，RIC条件下血浆仍然介导保护。此外，在大腿和手臂的RIC的终点没有发现差异。这些数据表明，RIC的定位和“剂量”不影响细胞保护，并进一步阐明了亚硝酸盐促进RIC依赖性保护的机制。
Remote Ischemic Conditioning (RIC), induced by brief cycles of ischemia and reperfusion, protects vital organs from a prolonged ischemic insult. While several biochemical mediators have been implicated in RIC's mechanism of action, it remains unclear whether the localization or “dose” of RIC affects the extent of protective signaling. In this randomized crossover study of healthy individuals, we tested whether the number of cycles of RIC and its localization (arm versus thigh) determines biochemical signaling and cytoprotection. Subjects received either arm or thigh RIC and then were crossed over to receive RIC in the other extremity. Blood flow, tissue perfusion, concentrations of the circulating protective mediator nitrite, and platelet mitochondrial function were measured after each RIC cycle. We found that plasma nitrite concentration peaked after the first RIC cycle and remained elevated throughout RIC. This plasma nitrite conferred cytoprotection in an in vitro myocyte model of hypoxia/reoxygenation. Notably, though plasma nitrite returned to baseline at 24 h, RIC conditioned plasma still mediated protection. Additionally, no difference in endpoints between RIC in thigh versus arm was found. These data demonstrate that localization and “dose” of RIC does not affect cytoprotection and further elucidate the mechanisms by which nitrite contributes to RIC-dependent protection.