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Asymmetric dimethylarginine at sea level is a predictive marker of hypoxic pulmonary arterial hypertension at high altitude

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dc.contributor.author Siques, Patricia
dc.contributor.author Brito, Julio
dc.contributor.author Schwedhelm, Edzard
dc.contributor.author Pena, Eduardo
dc.contributor.author León-Velarde, Fabiola
dc.contributor.author De La Cruz, Juan Jose
dc.contributor.author Boeger, Rainer H.
dc.contributor.author Hannemann, Juliane
dc.date.accessioned 2019-07-04T16:59:21Z
dc.date.available 2019-07-04T16:59:21Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/6727
dc.description.abstract Background: Prolonged exposure to altitude-associated chronic hypoxia (CH) may cause high-altitude pulmonary hypertension (HAPH). Chronic intermittent hypobaric hypoxia (CIH) occurs in individuals who commute between sea level and high altitude. CIH is associated with repetitive acute hypoxic acclimatization and conveys the long-term risk of HAPH. As nitric oxide (NO) regulates pulmonary vascular tone and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, we investigated whether ADMA concentration at sea level predicts HAPH among Chilean frontiers personnel exposed to 6 months of CIH. Methods: In this prospective study, 123 healthy army draftees were subjected to CIH (5 days at 3,550 m, 2 days at sea level) for 6 months. In 100 study participants with complete data, ADMA, symmetric dimethylarginine (SDMA), L-arginine, arterial oxygen saturation (SaO(2)), systemic blood pressure, and hematocrit were assessed at months 0 (sea level), 1, 4, and 6. Acclimatization to altitude was determined using the Lake Louise Score (LLS) and the presence of acute mountain sickness (AMS). Echocardiography was performed after 6 months of CIH in 43 individuals with either good (n = 23) or poor (n = 20) acclimatization. Results: SaO(2) acutely decreased at altitude and plateaued at 90% thereafter. ADMA increased and SDMA decreased during the study course. The incidence of AMS and the LLS was high after the first ascent (53 and 3.1 +/- 2.4) and at 1 month of CIH (47 and 3.0 +/- 2.6), but decreased to 20 and 1.4 +/- 2.0 at month 6 (both p < 0.001). Eighteen participants (42%) showed a mean pulmonary arterial pressure (mPAP) >25 mm Hg, out of which 9 (21%) were classified as HAPH (mPAP >= 30 mm Hg). ADMA at sea level was significantly associated with mPAP at high altitude in month 6 (R = 0.413; p = 0.007). In ROC analysis, a cutoff for baseline ADMA of 0.665 mu mol/L was determined to predict HAPH (mPAP > 30 mm Hg) with a sensitivity of 100% and a specificity of 63.6%. Conclusions: ADMA concentration increases during CIH. ADMA at sea level is an independent predictive biomarker of HAPH. SDMA concentration decreases during OH and shows no association with HAPH. Our data support a role of impaired NO-mediated pulmonary vasodilation in the pathogenesis of HAPH. en_US
dc.language.iso eng
dc.publisher Frontiers Media
dc.relation.ispartofseries Frontiers in Physiology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject 6 n,n' dimethylarginine en_US
dc.subject ADMA en_US
dc.subject adult en_US
dc.subject altitude en_US
dc.subject altitude acclimatization en_US
dc.subject altitude disease en_US
dc.subject arterial oxygen saturation en_US
dc.subject Article en_US
dc.subject Chile en_US
dc.subject chronic intermittent hypoxia en_US
dc.subject cohort analysis en_US
dc.subject diagnostic test accuracy study en_US
dc.subject Endothelium en_US
dc.subject high altitude pulmonary hypertension en_US
dc.subject human en_US
dc.subject human experiment en_US
dc.subject Hypobaric hypoxia en_US
dc.subject lung artery pressure en_US
dc.subject male en_US
dc.subject n(g),n(g) dimethylarginine en_US
dc.subject Nitric oxide en_US
dc.subject normal human en_US
dc.subject prognosis en_US
dc.subject pulmonary hypertension en_US
dc.subject receiver operating characteristic en_US
dc.subject Right ventricle en_US
dc.subject Risk prediction en_US
dc.subject SDMA en_US
dc.subject sea level en_US
dc.subject sensitivity and specificity en_US
dc.title Asymmetric dimethylarginine at sea level is a predictive marker of hypoxic pulmonary arterial hypertension at high altitude en_US
dc.type info:eu-repo/semantics/review
dc.identifier.doi https://doi.org/10.3389/fphys.2019.00651
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.08
dc.relation.issn 1664-042X

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