Altitude Sickness, Hypertension, Pulmonary
Conditions
Keywords
Acetazolamide, Methazolamide, Control of breathing, Hypoxic pulmonary vasoconstriction
Brief summary
The purpose of this proposal is to compare the physiological effects of acetazolamide (AZ) and methazolamide (MZ) on the control of breathing and hypoxic pulmonary vasoconstriction. The first objective is to assess the effects of AZ and MZ on the control of breathing in normoxia and hypoxia. To achieve this the ventilatory interaction between oxygen and carbon dioxide will be measured and effects compared between placebo, AZ, and MZ conditions. In addition, the isocapnic and poikilocapnic hypoxic ventilatory response and hypercapnic ventilatory response will be measured with each drug. The second objective is to assess the effects of AZ and MZ on the control of the pulmonary vasculature during hypoxia. Pulmonary pressure and cardiac output will be measured during 60 minutes of poikilocapnic hypoxia.
Interventions
Sponsors
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-40 years of age * regularly physically active * male
Exclusion criteria
* ex-smokers * pulmonary function \<80% of predicted * contraindications to carbonic anhydrase inhibitors (eg. severe or absolute glaucoma, adrenocortical insufficiency, hepatic insufficiency, renal insufficiency, sulfa allergy or an electrolyte imbalance such as hyperchloremic acidosis) * Obese (BMI\>30Kg/m2) * diuretic medication use * blood thinner use * anti-platelet drug use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ventilation | Baseline and 60 minutes of poikilocapnic hypoxia | To quantify the isocapnic hypoxic ventilatory response, the hypercapnic ventilatory response, and the hypercapnic hypoxic ventilatory response, ventilation will be measured throughout controlled changes in end-tidal gas levels. Each protocol will consist of 90s steps in end-tidal oxygen partial pressure from baseline through 65, 57, and 47 mmHg. For hypercapnic hypoxia, the end-tidal partial pressure for carbon dioxide will be increased from baseline to +6 mmHg for 7 minutes before reducing the end-tidal partial pressure of oxygen as above. The poikilocapnic hypoxic ventilatory response will be determined by measuring the change in ventilation from baseline throughout 60 minutes of poikilocapnic hypoxia (fraction of inspired oxygen = 0.12) |
| Change in pulmonary artery pressure | Baseline and 60 minutes of poikilocapnic hypoxia | Pulmonary artery systolic pressure (PASP) will be derived using the modified Bernoulli equation and the regurgitant velocity across the tricuspid valve. Estimates of right atrial pressure will be evaluated based upon the collapsibility index of the inferior vena cave during a sniff test. The pulmonary artery pressure response will be measured during 60 minutes of exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in cerebral blood velocity | Baseline and 60 minutes | To quantify the isocapnic hypoxic cerebral blood velocity response, the hypercapnic cerebral blood velocity response, and the hypercapnic hypoxic cerebral blood velocity response, cerebral blood velocity in the middle and posterior cerebral arteries will be measured throughout controlled changes in end-tidal gas levels. Each protocol will consist of 90s steps in end-tidal oxygen partial pressure from baseline through 65, 57, and 47 mmHg. For hypercapnic hypoxia, the end-tidal carbon dioxide partial pressure will be increased from baseline to +6 mmHg for 7 minutes before reducing the end-tidal oxygen partial pressure as above. The poikilocapnic hypoxic ventilatory response will be determined by measuring the change in ventilation from baseline throughout 60 minutes of poikilocapnic hypoxia (fraction of inspired oxygen = 0.12) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in heart rate | Baseline and 60 minutes | — |
| change in blood pressure | Baseline and 60 minutes | — |
| change in end-tidal oxygen and carbon dioxide partial pressure | Baseline and 60 minutes | — |
| Change in arterial oxygen saturation | Baseline and 60 minutes | — |
| change in arterial oxygen partial pressure | Baseline and 60 minutes | — |
| Change in pulmonary venous blood velocity | Baseline and 60 minutes of poikilocapnic hypoxia | Doppler ultrasound will be used to measure the velocity of blood draining from the pulmonary vein at baseline and throughout exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12) |
| Hemoglobin | Baseline | — |
| albumin | Baseline | — |
| iron | Baseline | — |
| Change in cardiac output | Baseline and 60 minutes of poikilocapnic hypoxia | Cardiac output will be determined using the aortic time integral velocity and the diameter of the aortic valve annulus. Data will be collected at baseline and throughout exposure to poikilocapnic hypoxia (fraction of inspired oxygen = 0.12) |
| Change in arterial carbon dioxide partial pressure | Baseline and 60 minutes | — |
| Change in arterial pH | Baseline and 60 minutes | — |
Countries
Canada
Outcome results
None listed