Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction and Exercise Capacity at High Altitude

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.

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 iloprost 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.

Baseline echo measurements, cardiac output, pulse oximetry will be taken. Subjects will then be given one dose of inhaled iloprost. Post-inhalation, the measurements will be repeated at rest and with exercise.

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: Unable to measure TR velocity Known liver disease Pregnancy Nitrates, cyclosporin, glyburide or other 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