Fan Ning, Liu Cun, Ren Ming
Graduate School of Qinghai University.
Qinghai Cardiovascular Hospital.
Medicine (Baltimore). 2020 Mar;99(11):e19292. doi: 10.1097/MD.0000000000019292.
The aim of the study was to provide a theoretical basis for the early diagnosis and prediction of acute altitude sickness, to provide a better entry mode for healthy people from plain areas to plateau areas, and to preliminarily clarify the possible mechanism of this approach.
We measured endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), nitric oxide (NO), and hypoxia-inducible factor 1 (HIF-1) levels in each sample and determined flow-mediated dilation (FMD) values using a portable OMRON color Doppler with a 7.0- to 12.0-MHz linear array probe. We used the Lewis Lake score to diagnose acute mountain sickness (AMS) and to stratify the disease severity.
We found no cases of AMS at any of the studied elevation gradients. We found significant differences in FMD values between individuals when at 400 m above sea level and when at 2200, 3200, and 4200 m above sea level (P < .05) but found no significant differences among those at 2200, 3200, and 4200 m. Our variance analysis showed that serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in individuals at ≥3000 m and those at subplateau and plain areas (<3000 m) significantly differed (P < .05). The level of these factors also significantly differed between individuals at elevation gradients of plateau areas (3260 m vs 4270 m) (P < .05). We found no significant differences in serum ET-1, VEGF, and ADMA levels between individuals at the plateau (2260 m) and plain (400 m) areas (P > .05). NO and HIF-1 levels were significantly different in serum samples from individuals between the plateau (2260 m) and plain (400 m) areas (P < .05). However, with increasing altitude, the NO level gradually increased, whereas ET-1, ADMA, VEGF, and HIF-1 levels showed a decreasing trend. With the increase of altitude, there is no correlation between the trend of FMD and hematologic-related factors such as VEGF, NO, and HIF-1.
A healthy young male population ascending to a high-altitude area experiences a low incidence of AMS. Entering an acute plateau exposure environment from different altitude gradients may weaken the effect of acute highland exposure on vascular endothelial dysfunction in healthy individuals. Changes in serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in healthy young men may be related to the body's self-regulation and protect healthy individuals from AMS. A short stay in a subplateau region may initiate an oxygen-free preconditioning process in healthy individuals, thereby protecting them from AMS. Noninvasive brachial artery endothelial function test instead of the detection of invasive hematologic-related factors for early diagnosis and prediction of the occurrence and severity of acute high-altitude disease is still lack of sufficient theoretical basis.
本研究旨在为急性高原病的早期诊断和预测提供理论依据,为平原地区健康人群进入高原地区提供更好的进入模式,并初步阐明该方法的可能机制。
我们测量了每个样本中内皮素-1(ET-1)、不对称二甲基精氨酸(ADMA)、血管内皮生长因子(VEGF)、一氧化氮(NO)和缺氧诱导因子1(HIF-1)的水平,并使用带有7.0至12.0 MHz线性阵列探头的便携式欧姆龙彩色多普勒仪测定血流介导的血管舒张(FMD)值。我们使用Lewis Lake评分来诊断急性高山病(AMS)并对疾病严重程度进行分层。
在任何研究的海拔梯度下,我们均未发现AMS病例。我们发现个体在海拔400米时与在海拔2200、3200和4200米时的FMD值存在显著差异(P<0.05),但在海拔2200、3200和4200米的个体之间未发现显著差异。我们的方差分析表明,海拔≥3000米的个体与亚高原和平原地区(<3000米)的个体血清ET-1、VEGF、ADMA、NO和HIF-1水平存在显著差异(P<0.05)。这些因素的水平在高原地区不同海拔梯度(3260米与4270米)的个体之间也存在显著差异(P<0.05)。我们发现高原(2260米)和平原(400米)地区个体的血清ET-1、VEGF和ADMA水平无显著差异(P>0.05)。高原(2260米)和平原(400米)地区个体血清样本中的NO和HIF-1水平存在显著差异(P<0.05)。然而,随着海拔升高,NO水平逐渐升高,而ET-1、ADMA、VEGF和HIF-1水平呈下降趋势。随着海拔升高,FMD趋势与VEGF、NO和HIF-1等血液学相关因素之间无相关性。
健康年轻男性人群进入高海拔地区时AMS发病率较低。从不同海拔梯度进入急性高原暴露环境可能会减弱急性高原暴露对健康个体血管内皮功能障碍的影响。健康年轻男性血清ET-1、VEGF、ADMA、NO和HIF-1水平的变化可能与机体的自我调节有关,并保护健康个体免受AMS侵害。在亚高原地区短暂停留可能会启动健康个体的无氧预处理过程,从而保护他们免受AMS侵害。使用无创肱动脉内皮功能测试而非检测侵入性血液学相关因素来早期诊断和预测急性高原病的发生和严重程度仍缺乏充分的理论依据。