Savina Yann, Pichon Aurélien P, Lemaire Lucas, Howe Connor A, Ulliel-Roche Mathilde, Skinner Sarah, Nader Elie, Guillot Nicolas, Stauffer Émeric, Roustit Matthieu, Hancco Ivan, Robach Paul, Esteve François, Pialoux Vincent, Perger Elisa, Parati Gianfranco, Ainslie Philip N, Doutreleau Stéphane, Connes Philippe, Verges Samuel, Brugniaux Julien V
HP2 laboratory, Univ. Grenoble Alpes, INSERM, CHU Grenoble Alpes, Grenoble, France.
Laboratory Mobility, Aging & Exercise (MOVE, EA6314), Faculty of Sport Sciences, University of Poitiers, Poitiers, France.
Lancet Reg Health Am. 2024 Sep 25;38:100887. doi: 10.1016/j.lana.2024.100887. eCollection 2024 Oct.
Since vascular responses to hypoxia in both healthy high-altitude natives and chronic mountain sickness (a maladaptive high-altitude pathology characterised by excessive erythrocytosis and the presence of symptoms-CMS) remain unclear, the role of inflammation and oxidative/nitrosative stress on the endothelium- and - responses in both the micro- and macrocirculation, in healthy Andeans at different altitudes and in CMS patients, was examined.
94 men were included: 18 lowlanders (LL), 38 healthy highlanders permanently living at 3800 m (n = 21-HL-3800) or in La Rinconada, the highest city in the world (5100-5300 m) (n = 17-HL-5100/No CMS). Moreover, 14 participants with mild (Mild CMS) and 24 with moderate to severe CMS (Mod/Sev CMS) were recruited. All undertook two reactivity tests: i) local thermal hyperaemia (microcirculation) and ii) flow-mediated dilation (macrocirculation). Endothelium- function (glyceryl trinitrate) was also assessed only in La Rinconada.
Conductance and skin blood flow velocity during the microcirculation test, as well as macrocirculation progressively decreased with altitude (LL > HL-3800 > HL-5100/No CMS). CMS also induced a decrease in macrocirculation (HL-5100/No CMS > Mild CMS = Mod/Sev CMS), while glyceryl trinitrate restored vascular function. Both oxidative stress and nitric oxide metabolites increased with altitude only. Principal component analysis revealed that increasing inflammation with altitude was associated with a progressive decline in both micro- and macrovascular function in healthy highlanders.
Both micro and macrovascular function are affected by chronic exposure to hypoxia, the latter being further compounded by CMS.
The "Fonds de dotation AGIR pour les maladies chroniques", the "Air Liquide Foundation", and the "French National Research Agency".
由于健康的高海拔原住民和慢性高山病（一种以红细胞增多和出现症状为特征的适应性不良的高海拔病理状态——CMS）对缺氧的血管反应仍不清楚，因此研究了炎症以及氧化/亚硝化应激在不同海拔的健康安第斯人群和CMS患者的微循环和大循环中对内皮功能及血管反应的作用。
纳入94名男性：18名低地居民（LL），38名永久居住在3800米的健康高海拔居民（n = 21 - HL - 3800）或居住在世界最高城市拉林科纳达（海拔5100 - 5300米）的居民（n = 17 - HL - 5100/无CMS）。此外，招募了14名轻度CMS患者（轻度CMS）和24名中度至重度CMS患者（中度/重度CMS）。所有人都进行了两项反应性测试：i）局部热充血（微循环）和ii）血流介导的血管舒张（大循环）。仅在拉林科纳达评估了内皮功能（硝酸甘油）。
微循环测试期间的电导和皮肤血流速度以及大循环功能随海拔升高而逐渐降低（LL > HL - 3800 > HL - 5100/无CMS）。CMS也导致大循环功能下降（HL - 5100/无CMS > 轻度CMS = 中度/重度CMS），而硝酸甘油可恢复血管功能。仅氧化应激和一氧化氮代谢产物随海拔升高而增加。主成分分析显示，随着海拔升高炎症增加与健康高海拔居民的微血管和大血管功能逐渐下降有关。
慢性缺氧会影响微血管和大血管功能，而CMS会使后者进一步恶化。
“慢性疾病捐赠基金AGIR”、“液化空气基金会”和“法国国家研究机构”。
