Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, Wales; Sondes Moléculaires en Biologie et Stress Oxydant, Institut de Chimie Radicalaire, Centre National de la Recherche Scientifique UMR 7273, Aix-Marseille University, France.
Department of Cardiology, University Hospital of Bern, Bern, Switzerland.
Chest. 2013 Feb 1;143(2):444-451. doi: 10.1378/chest.12-0728.
Acute exposure to high altitude stimulates free radical formation in lowlanders, yet whether this persists during chronic exposure in healthy, well-adapted and maladapted highlanders suffering from chronic mountain sickness (CMS) remains to be established.
Oxidative-nitrosative stress (as determined by the presence of the biomarkers ascorbate radical [A •- ], via electron paramagnetic resonance spectroscopy, and nitrite [NO 2 2 ], via ozone-based chemiluminescence) was assessed in venous blood of 25 male highlanders in Bolivia living at 3,600 m with CMS (n 5 13, CMS 1 ) and without CMS (n 5 12, CMS 2 ). Twelve age- and activity-matched, healthy, male lowlanders were examined at sea level and during acute hypoxia. We also measured fl ow-mediated dilatation (FMD), arterial stiffness defined by augmentation index normalized for a heart rate of 75 beats/min (AIx-75), and carotid intima-media thickness (IMT).
Compared with normoxic lowlanders, oxidative-nitrosative stress was moderately increased in the CMS 2 group ( P , .05), as indicated by elevated A •- (3,191 457 arbitrary units [AU] vs 2,640 445 AU) and lower NO 2 2 (206 55 nM vs 420 128 nM), whereas vascular function remained preserved. This was comparable to that observed during acute hypoxia in lowlanders in whom vascular dysfunction is typically observed. In contrast, this response was markedly exaggerated in CMS 1 group (A •- , 3,765 429 AU; NO 2 2 , 148 50 nM) compared with both the CMS 2 group and lowlanders ( P , .05). This was associated with systemic vascular dysfunction as indicated by lower ( P , .05 vs CMS 2 ) FMD (4.2% 0.7% vs 7.6% 1.7%) and increased AIx-75 (23% 8% vs 12% 7%) and carotid IMT (714 127 m M vs 588 94 m M).
Healthy highlanders display a moderate, sustained elevation in oxidative-nitrosative stress that, unlike the equivalent increase evoked by acute hypoxia in healthy lowlanders, failed to affect vascular function. Its more marked elevation in patients with CMS may contribute to systemic vascular dysfunction.
急性暴露于高海拔会刺激低海拔人群自由基的形成，但在健康、适应良好和适应不良的高海拔人群中慢性暴露时，自由基是否持续存在，这些人群患有慢性高原病（CMS），这仍有待确定。
通过电子顺磁共振波谱（EPR）测定静脉血中抗坏血酸自由基（A •- ）的存在来评估氧化-硝化应激（作为生物标志物），通过臭氧化学发光法测定亚硝酸盐[NO 2 2 ]的存在来评估氧化-硝化应激（作为生物标志物）。25 名男性高海拔居民在玻利维亚海拔 3600 米处患有 CMS（n 5 13，CMS 1 ）和无 CMS（n 5 12，CMS 2 ）。12 名年龄和活动相匹配的健康男性低海拔居民在海平面和急性缺氧时接受了检查。我们还测量了血流介导的扩张（FMD）、心率为 75 次/分时的增强指数归一化（AIx-75）定义的动脉僵硬度，以及颈动脉内膜中层厚度（IMT）。
与低海拔常氧者相比，CMS 2 组的氧化-硝化应激中度增加（P,.05），表现为 A •- 升高（3191457 个任意单位[AU]与 2640445 AU）和 NO 2 2 降低（20655 nM 与 420128 nM），而血管功能保持不变。这与低海拔人群急性缺氧时观察到的情况相似，在低海拔人群中，急性缺氧通常会导致血管功能障碍。相比之下，CMS 1 组的这种反应明显更为剧烈（A •- ，3765429 AU；NO 2 2 ，14850 nM），与 CMS 2 组和低海拔人群相比（P,.05）。这与全身血管功能障碍有关，表现为 FMD 降低（P,.05 vs CMS 2 ）（4.2% 0.7% vs 7.6% 1.7%）和 AIx-75 升高（23% 8% vs 12% 7%）和颈动脉 IMT 增加（714127 m M 与 58894 m M）。
健康的高海拔居民表现出适度、持续的氧化-硝化应激升高，与急性低氧在健康低海拔人群中引起的同等升高不同，这种升高并未影响血管功能。其在 CMS 患者中更为明显的升高可能导致全身血管功能障碍。
