Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction at Altitude

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction With Exercise at High Altitude

Conditions
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Hypoxic Pulmonary Vasoconstriction

Intervention / Treatment
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* Drug: iloprost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 - 80 years Healthy physically active males or females Have readily measurable tricuspid regurgitation (TR) peak systolic velocity by continuous wave Doppler ultrasound Exclusion Criteria: Known liver disease Pregnancy 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Iloprost and placebo<br>Each participant will undergo testing at sea level and altitude after inhalation of iloprost and placebo, sequence is randomly assigned. | Drug: iloprost<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise capacity, pulmonary artery systolic pressure, cardiac output, oxygen saturation |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate, tissue Doppler echocardiographic measurements |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iloprost, hypoxic, pulmonary, vasoconstriction, altitude