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Hypoxia Impairs Endothelial Function in HAPEs

This study has been completed.
Sponsor:
Information provided by:
Heidelberg University
ClinicalTrials.gov Identifier:
NCT00176007
First received: September 10, 2005
Last updated: NA
Last verified: June 2005
History: No changes posted

September 10, 2005
September 10, 2005
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Hypoxia Impairs Endothelial Function in HAPEs
Hypoxia Impairs Systemic Endothelial Function in Individuals Prone to High-Altitude Pulmonary Edema.

Aim of the study is to investigate the function of the systemic vascular endothelium in individuals susceptible to high-altitude pulmonary oedema during normoxia and normobaric hypoxia.

Rationale: High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung. Objectives: We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature. Methods: During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects. Main Results: Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02). Conclusions: Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.

Interventional
Phase 1
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind
Primary Purpose: Educational/Counseling/Training
Healthy
Procedure: Hypoxia
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
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Inclusion Criteria:

Healthy, male volunteers, age: 18-55

- Able and willing to give written informed consent

Exclusion Criteria:

  • Known condition causing endothelial dysfunction (e.g. diabetes, hyperlipidaemia, arterial hypertension, smoking, hyperhomocysteinaemia)
  • Regular medication and/or treatment with drugs within the last 4 weeks (exclusion has to be decided in each case)
  • Acute or chronic illness
  • Participation in clinical trial/blood donation within 2 month before the study
  • Nicotine, drug and/or alcohol abuse.
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
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NCT00176007
A001
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Heidelberg University
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Principal Investigator: Walter E Haefeli, MD Heidelberg University
Heidelberg University
June 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP