Hypoxic Pulmonary Vasoconstriction
Conditions
Keywords
iloprost, hypoxic, pulmonary, vasoconstriction, altitude
Brief summary
The objective of this study is to determine if single dose administration of inhaled iloprost will reduce pulmonary artery pressure, reduce hypoxic pulmonary vasoconstriction and improve arterial oxygenation at rest and during exercise at high altitude.
Detailed description
Three major pathways in addition to oxygen modulate pulmonary vascular tone: 1) nitric oxide, 2) endothelin, and 3) prostacyclin. Considerable animal data support the role of the prostacyclin pathway in modulating hypoxic pulmonary vasoconstriction. In humans, prostacyclin and its analogs are important therapeutic agents in the treatment of pulmonary arterial hypertension (PAH). Despite the animal data and human data in PAH there is very little information about the use of to relieve hypoxic pulmonary vasoconstriction in healthy humans. Inhaled iloprost is an ideal agent to study the prostacyclin pathway due to its short duration of action (30-90 min) and elimination half-life of only 20-30 min. Individuals already participating in the Nepal Medex 2008 trip will be invited to participate in this research. Participants will be healthy active females or males, between 18-80 years of age, without known pregnancy or liver disease, who have a readily measurable tricuspid regurgitant velocity by Doppler echocardiography. If possible, we will attempt to identify a cohort of HAPE susceptible patients. Participants will undergo evaluation both at sea level (baseline) and at high altitude. Baseline (low altitude) testing will be performed in Bangor, North Wales, UK, and will include evaluation of pulmonary artery systolic pressures, cardiac output, and oxygen saturation at rest and during submaximal exercise before and after inhalation of iloprost. This strategy will then be repeated at an altitude of approximately 5000 meters in the Dhaulagiri region of Nepal.
Interventions
DRUGiloprost
A dose of inhaled iloprost (or placebo) will be given once at baseline and then at altitude. Measurements will be obtained before and after inhalation. Patients will then cross over and be given a dose of placebo (or iloprost)and measurements will be repeated.
Sponsors
Loma Linda University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age: 18 - 80 years 2. Healthy physically active males or females 3. Have readily measurable tricuspid regurgitation (TR) peak systolic velocity by continuous wave Doppler ultrasound
Exclusion criteria
1. Known liver disease 2. Pregnancy 3. Medications that in the opinion of the investigators could place subjects at increased risk of complications Any other medical condition that in the opinion of the investigators would place the subject at high risk
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Exercise capacity, pulmonary artery systolic pressure, cardiac output, oxygen saturation | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Heart rate, tissue Doppler echocardiographic measurements | 6 months |
Countries
United States
Outcome results
None listed