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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Room Air Rebreathe | Sham Comparator | Rebreathe protocol will be completed with a room air syringe rather than CO |
|
| CO Rebreathe | Experimental | Rebreathe protocol will be completed with Carbon Monoxide |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carbon monoxide rebreathe | Other | Carbon monoxide exposure to increase blood (Carboxyhemoglobin) COHb safely to ~10% |
|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sean van Diepen, MD, MSc | University of Alberta | Principal Investigator |
| Craig Steinback, PhD | University of Alberta | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alberta | Edmonton | Alberta | T6G 2R3 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25330393 | Background | Basnyat B. High altitude pilgrimage medicine. High Alt Med Biol. 2014 Dec;15(4):434-9. doi: 10.1089/ham.2014.1088. | |
| 30764644 | Background | Rezk-Hanna M, Mosenifar Z, Benowitz NL, Rader F, Rashid M, Davoren K, Moy NB, Doering L, Robbins W, Sarna L, Li N, Chang LC, Elashoff RM, Victor RG. High Carbon Monoxide Levels from Charcoal Combustion Mask Acute Endothelial Dysfunction Induced by Hookah (Waterpipe) Smoking in Young Adults. Circulation. 2019 May 7;139(19):2215-2224. doi: 10.1161/CIRCULATIONAHA.118.037375. |
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| ID | Term |
|---|---|
| D000783 | Aneurysm |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D009599 | Nitroprusside |
| D010656 | Phenylephrine |
| ID | Term |
|---|---|
| D005292 | Ferricyanides |
| D003486 | Cyanides |
| D000838 | Anions |
| D007477 | Ions |
| D004573 |
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Participants will partake in both room air and CO exposure on 2 separate visits.
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Participant will not be aware of which rebreathe treatment (CO or Room Air) they are receiving.
| Sodium Nitroprusside | Drug | Bolus Sodium Nitroprusside (SNP) injection for endothelium-independent vasodilation measure |
|
|
| Phenylephrine Hydrochloride | Drug | Bolus Phenylephrine injection for observe α1-mediated vasoconstriction during mild exercise |
|
| 29334505 | Background | Choi BG, Lee J, Kim SW, Lee MW, Baek MJ, Ryu YG, Choi SY, Byun JK, Mashaly A, Park Y, Jang WY, Kim W, Choi JY, Park EJ, Na JO, Choi CU, Lim HE, Kim EJ, Park CG, Seo HS, Oh DJ, Rha SW. The association of chronic air pollutants with coronary artery spasm, vasospastic angina, and endothelial dysfunction. Coron Artery Dis. 2018 Jun;29(4):336-343. doi: 10.1097/MCA.0000000000000603. |
| 21787716 | Background | Weber LP, Al-Dissi A, Marit JS, German TN, Terletski SD. Role of carbon monoxide in impaired endothelial function mediated by acute second-hand tobacco, incense, and candle smoke exposures. Environ Toxicol Pharmacol. 2011 May;31(3):453-9. doi: 10.1016/j.etap.2011.02.008. Epub 2011 Feb 26. |
| 31677355 | Background | Tymko MM, Tremblay JC, Bailey DM, Green DJ, Ainslie PN. The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations. J Physiol. 2019 Dec;597(24):5759-5776. doi: 10.1113/JP277191. Epub 2019 Nov 28. |
| Electrolytes |
| D007287 | Inorganic Chemicals |
| D005290 | Ferric Compounds |
| D058085 | Iron Compounds |
| D006856 | Hydrogen Cyanide |
| D017672 | Nitrogen Compounds |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |