Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction and Exercise Capacity at High Altitude
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.
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 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.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Conditions
Hypoxic Pulmonary Vasoconstriction
Intervention
iloprost
Location
Jerry L. Pettis VA Medical Center
Loma Linda
California
United States
92357
Status
Recruiting
Source
VA Loma Linda Health Care System
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00708565
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
4,5-dihydro-1-(3-(trifluoromethyl)phenyl)-1h-pyrazol-3-amine
A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
Iloprost
An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of EPOPROSTENOL, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation.
Misonidazole
A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic.
Persistent Fetal Circulation Syndrome
A syndrome of persistent PULMONARY HYPERTENSION in the newborn infant (INFANT, NEWBORN) without demonstrable HEART DISEASES. This neonatal condition can be caused by severe pulmonary vasoconstriction (reactive type), hypertrophy of pulmonary arterial muscle (hypertrophic type), or abnormally developed pulmonary arterioles (hypoplastic type). The newborn patient exhibits CYANOSIS and ACIDOSIS due to the persistence of fetal circulatory pattern of right-to-left shunting of blood through a patent ductus arteriosus (DUCTUS ARTERIOSUS, PATENT) and at times a patent foramen ovale (FORAMEN OVALE, PATENT).
Pulmonary Heart Disease
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.
Clinical Trials
Effects of Iloprost on Hypoxic Pulmonary Vasoconstriction at 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 a...
Inhaled nitrous oxide (iNO) will be compared to aerosolized iloprost (ILO) in pediatric patients after cardiac surgery with pulmonary hypertension. The hypothesis is that iloprost is more...
The investigators believe that iloprost will improve gas exchange in COPD patients with pulmonary hypertension.
Safety Follow-up Study of Inhaled Iloprost in Patients With Pulmonary Hypertension
The aim of this study is to monitor long-term safety and tolerability of iloprost aerosol inhalation therapy in patients suffering from pulmonary hypertension.
Treatment of Elevated Arterial Pulmonary Pressure With Inhaled Iloprost
The purpose of this study is to determine if iloprost is effective in the treatment of elevated arterial pulmonary pressure in children with ventilator treated respiratory distress syndrom...
PubMed Articles
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Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. B...
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Redox signaling and reactive oxygen species in hypoxic pulmonary vasoconstriction.
Hypoxic pulmonary vasoconstriction (HPV) is an essential physiological mechanism of the lung that matches blood perfusion with alveolar ventilation to optimize gas exchange. Perturbations of HPV, as m...
