The Effect of Carbonic Anhydrase Inhibitors on the Pulmonary System Response to Hypoxia
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Change in ventilation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •18-40 years of age
- •regularly physically active
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.
Arms & Interventions
Acetazolamide
Participants will be dosed 250mg Acetazolamide (p.o.) three times per day for two days prior to and a single dose on the day of study.
Intervention: Acetazolamide (Drug)
Methazolamide
Participants will be dosed 100mg Methazolamide (p.o.) twice daily separated by a placebo for two days prior to and a single dose on the day of study. The placebo dose is provided to match the dosing schedule between conditions.
Intervention: Methazolamide (Drug)
Placebo
Participants will take (p.o.) placebo pills three times per day for two days prior to and a single dose on the day of study.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in ventilation
Time Frame: 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
Time Frame: 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 Outcomes
- Change in cerebral blood velocity(Baseline and 60 minutes)