PMID- 31191349
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - Asymmetric Dimethylarginine at Sea Level Is a Predictive Marker of Hypoxic 
      Pulmonary Arterial Hypertension at High Altitude.
PG  - 651
LID - 10.3389/fphys.2019.00651 [doi]
LID - 651
AB  - 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 mumol/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 CIH and shows no association with HAPH. Our 
      data support a role of impaired NO-mediated pulmonary vasodilation in the 
      pathogenesis of HAPH.
FAU - Siques, Patricia
AU  - Siques P
AD  - Institute of Health Studies, Universidad Arturo Prat, Iquique, Chile.
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and its Health Sequelae, Hamburg, Germany and Iquique, Chile.
FAU - Brito, Julio
AU  - Brito J
AD  - Institute of Health Studies, Universidad Arturo Prat, Iquique, Chile.
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and its Health Sequelae, Hamburg, Germany and Iquique, Chile.
FAU - Schwedhelm, Edzard
AU  - Schwedhelm E
AD  - Institute of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Pena, Eduardo
AU  - Pena E
AD  - Institute of Health Studies, Universidad Arturo Prat, Iquique, Chile.
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and its Health Sequelae, Hamburg, Germany and Iquique, Chile.
FAU - Leon-Velarde, Fabiola
AU  - Leon-Velarde F
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and its Health Sequelae, Hamburg, Germany and Iquique, Chile.
AD  - Department of Biological and Physiological Sciences, Facultad de Ciencias y 
      Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peru.
FAU - De La Cruz, Juan Jose
AU  - De La Cruz JJ
AD  - Department of Preventive Medicine and Public Health, Universidad Autonoma de 
      Madrid, Madrid, Spain.
FAU - Boger, Rainer H
AU  - Boger RH
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and its Health Sequelae, Hamburg, Germany and Iquique, Chile.
AD  - Institute of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Hannemann, Juliane
AU  - Hannemann J
AD  - Institute DECIPHER, German-Chilean Institute for Research on Pulmonary Hypoxia 
      and its Health Sequelae, Hamburg, Germany and Iquique, Chile.
AD  - Institute of Clinical Pharmacology and Toxicology, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20190527
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6545974
OTO - NOTNLM
OT  - ADMA
OT  - SDMA
OT  - endothelium
OT  - hypobaric hypoxia
OT  - nitric oxide
OT  - right ventricle
OT  - risk prediction
EDAT- 2019/06/14 06:00
MHDA- 2019/06/14 06:01
PMCR- 2019/05/27
CRDT- 2019/06/14 06:00
PHST- 2019/02/01 00:00 [received]
PHST- 2019/05/08 00:00 [accepted]
PHST- 2019/06/14 06:00 [entrez]
PHST- 2019/06/14 06:00 [pubmed]
PHST- 2019/06/14 06:01 [medline]
PHST- 2019/05/27 00:00 [pmc-release]
AID - 10.3389/fphys.2019.00651 [doi]
PST - epublish
SO  - Front Physiol. 2019 May 27;10:651. doi: 10.3389/fphys.2019.00651. eCollection 
      2019.