Yann Savina , Aurélien P. Pichon , Lucas Lemaire , Connor A. Howe , Mathilde Ulliel-Roche , Sarah Skinner , Elie Nader , Nicolas Guillot , Émeric Stauffer , Matthieu Roustit , Ivan Hancco , Paul Robach , François Esteve , Vincent Pialoux , Elisa Perger , Gianfranco Parati , Philip N. Ainslie , Stéphane Doutreleau , Philippe Connes , Samuel Verges , Julien V. Brugniaux
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引用次数: 0
Abstract
Background
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-dependent and -independent responses in both the micro- and macrocirculation, in healthy Andeans at different altitudes and in CMS patients, was examined.
Methods
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-independent function (glyceryl trinitrate) was also assessed only in La Rinconada.
Findings
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.
Interpretation
Both micro and macrovascular function are affected by chronic exposure to hypoxia, the latter being further compounded by CMS.
Funding
The “Fonds de dotation AGIR pour les maladies chroniques”, the “Air Liquide Foundation”, and the “French National Research Agency”.
期刊介绍:
The Lancet Regional Health – Americas, an open-access journal, contributes to The Lancet's global initiative by focusing on health-care quality and access in the Americas. It aims to advance clinical practice and health policy in the region, promoting better health outcomes. The journal publishes high-quality original research advocating change or shedding light on clinical practice and health policy. It welcomes submissions on various regional health topics, including infectious diseases, non-communicable diseases, child and adolescent health, maternal and reproductive health, emergency care, health policy, and health equity.