Decrease of asymmetric dimethylarginine predicts acute mountain sickness

Each year, 40 million tourists worldwide are at risk of getting acute mountain sickness (AMS), because they travel to altitudes of over 2500 m. As asymmetric dimethylarginine (ADMA) is a nitric oxide synthase (NOS) inhibitor, it should increase pulmonary artery pressure (PAP) and raise the risk of acute mountain sickness and high-altitude pulmonary edema (HAPE). With this in mind, we investigated whether changes in ADMA levels (Δ-ADMA) at an altitude of 4000 m can predict an individual's susceptibility to AMS or HAPE.

Twelve subjects spent two nights in a hypobaric chamber, the first night without exposure to altitude conditions and the second night at a simulated altitude of 4000 m. At identical time points during both nights (after 2, 5, and 11 hours), we determined ADMA serum levels, PAP by Doppler echocardiography and estimated hypoxia related symptoms by Lake Louise Score (LLS).

Contrary to our initial hypothesis, subjects with a marked increase in ADMA at 4000 m showed PAP levels below the critical threshold for HAPE and were not affected by AMS. By contrast, subjects with a decrease in ADMA suffered from AMS and had PAP levels above 40 mmHg. After 2 hours of hypoxia we found a significant relationship between Δ-PAP t(2) (Spearmans ρ = 0.30, p ≤ 0.05) respectively Δ-ADMA t(2) (ρ = -0.92, p ≤ 0.05) and LLS.

After 2 hours of hypoxia, the Δ-ADMA (positive or negative) can predict an LLS of >5 with a sensitivity of 80% and a specificity of 100% and can help assess the risk of an increase in PAP to more than 40 mmHg and thus the risk of HAPE (ϕ coefficient: 0.69; p ≤ 0.05).