Hypoxia Impairs Endothelial Function in HAPEs

Heidelberg University

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Procedure: Hypoxia

Study type

Interventional

Funder types

Other

Identifiers

NCT00176007

A001

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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.