Hypoxia Impairs Endothelial Function in HAPEs

Healthy Clinical Trial

Official title:

Hypoxia Impairs Systemic Endothelial Function in Individuals Prone to High-Altitude Pulmonary Edema.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00176007
• Other study ID #: A001
• Status: Completed
• Phase: Phase 1
• First received: September 10, 2005
• Last updated: September 10, 2005

Study information

• Verified date: June 2005
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind, Primary Purpose: Educational/Counseling/Training

Related Conditions & MeSH terms

• Healthy

Intervention

Procedure:
• Hypoxia

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University