The Impact of Carbon Monoxide and Altitude on Vascular Function

Study Overview
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Brief Summary
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The CarMA (Carbon Monoxide and Altitude) Study aims to observe the vascular effects of carbon monoxide exposure at low and high altitudes.

Detailed Description
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Each year, millions of people make journeys from low altitude regions to high altitude for recreation, travel, and religious pilgrimage. Carbon monoxide (CO) is commonly associated with cigarette smoke, exhaust fumes, and is viewed as a life-threatening toxic gas. Exposure to CO occurs during travel to and during activities common in high-altitude travel and pilgrimage including vehicle fumes, incense, and second-hand smoke exposure. High altitude exposure and CO exposure have been observed independently to have complex and opposing effects on vascular endothelial function. Observation of these stimuli together in a controlled environment may allow for further understanding of the underlying mechanisms of vascular physiology and adaptations to both high-altitude and CO exposure. The CarMA (Carbon Monoxide and Altitude) Study aims to observe the vascular effects of carbon monoxide exposure at low and high altitudes. Recently, other studies have showed a significant improvement in flow mediated dilation (FMD) with acute exposure to low levels of CO To date, no research has been presented concerning the effect of CO on vascular function at altitude. The present study aims to observe the effect of acute carbon monoxide exposure on 1) flow mediated dilation, 2) conduit artery flow in exercise induced reactive hyperemia at sea level and at altitude, and 3) the effect of CO on vascular function in a high altitude dwelling (sherpa) population.

Official Title
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The Impact of Carbon Monoxide and Altitude on Vascular Function

Conditions
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Vasodilation, Vasoconstriction

Intervention / Treatment
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* Other: Carbon monoxide rebreathe
* Drug: Sodium Nitroprusside
* Drug: Phenylephrine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 18-50 years No medical history of cardiovascular, respiratory, nervous system, or metabolic disease. Women must be pre-menopausal. Exclusion Criteria: Participants with any known cardiovascular, respiratory, nervous system, or metabolic disease. Having travelled above 2,000m within 1 month of testing at low and high altitude. Women who are pregnant, confirmed by a pregnancy test. Women who are post-menopausal. Participants that are classified as obese (body mass index > 30 kg/m2). Participants who are current daily smokers. Participants that are currently taking monoamine (MAO) inhibitors, or tricyclic antidepressants.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will partake in both room air and CO exposure on 2 separate visits.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Room Air Rebreathe<br>Rebreathe protocol will be completed with a room air syringe rather than CO | Drug: Sodium Nitroprusside<br>* Bolus Sodium Nitroprusside (SNP) injection for endothelium-independent vasodilation measure<br>* Other names: Nipride;Drug: Phenylephrine Hydrochloride<br>* Bolus Phenylephrine injection for observe α1-mediated vasoconstriction during mild exercise<br>|
| Experimental: CO Rebreathe<br>Rebreathe protocol will be completed with Carbon Monoxide | Other: Carbon monoxide rebreathe<br>* Carbon monoxide exposure to increase blood (Carboxyhemoglobin) COHb safely to  10%<br>* Other names: Schmidt-Prommer blood volume test;Drug: Sodium Nitroprusside<br>* Bolus Sodium Nitroprusside (SNP) injection for endothelium-independent vasodilation measure<br>* Other names: Nipride;Drug: Phenylephrine Hydrochloride<br>* Bolus Phenylephrine injection for observe α1-mediated vasoconstriction during mild exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brachial artery diameter (assessed via ultrasound) following release of arterial occlusion | Change in brachial artery diameter (assessed via ultrasound) following release of arterial occlusion | 15 minutes | 
| Blood flow within the brachial artery during rhythmic handgrip exercise. | Blood flow within the brachial artery during rhythmic handgrip exercise. | 15 minutes | 
| Change in brachial artery conductance following an infusion of phenylephrine | Change in brachial artery conductance following an infusion of phenylephrine | 5 min |