The Impact of Carbon Monoxide and Altitude on Vascular Function (CarMA)

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

Study Overview

• Status: Completed
• Conditions: Vasodilation; Vasoconstriction
• Intervention / Treatment: Drug: Sodium Nitroprusside; Drug: Phenylephrine Hydrochloride; Other: Carbon monoxide rebreathe

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R3
      • University of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alberta
• Investigators: Principal Investigator: Sean van Diepen, MD, MSc, University of Alberta; Principal Investigator: Craig Steinback, PhD, University of Alberta

Publications and helpful links

General Publications

• Basnyat B. High altitude pilgrimage medicine. High Alt Med Biol. 2014 Dec;15(4):434-9. doi: 10.1089/ham.2014.1088.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2021
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): May 18, 2022

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Antimetabolites; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Gasotransmitters; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nitric Oxide Donors; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Carbon Monoxide; Phenylephrine; Oxymetazoline; Nitroprusside
• Other Study ID Numbers: Pro00096251

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No