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Attenuation of hypoxic pulmonary vasoconstriction by acetazolamide and methazolamide : a randomized crossover study.

University of British Columbia

Context: Acetazolmaide (AZ) is used in the prophylactic treatment of altitude illnesses. AZ is also known to attenuate HPV and increase alveolar ventilation. Methazolamide (MZ) is an analog to AZ and its effects on ventilation and HPV are unknown. Objective. To determine if MZ can improve oxygenation and attenuate HPV to a similar extent as AZ in healthy humans exposed to poikilocapnic hypoxia. Design, Setting, Participants and Interventions: A randomized, placebo controlled, double-blinded trial was performed in healthy participants at the Cardiopulmonary Lab for Experimental and Applied Physiology. Prior to each of the three experimentation days, participants were administered one of three treatments (AZ, MZ, & placebo) at random for two days. Each treatment was separated by a 10-day washout period to avoid contamination from previous trials. During each trial, participants were exposed to poikilocapnic hypoxia (FIO2 ≈ 0.12) for 60 minutes. Primary Outcome Measures: Partial pressure of alveolar O₂ (PAO₂) represented oxygenation while pulmonary artery systolic pressure (PASP) and total pulmonary resistance (TPR) were chosen to represent the HPV response. Results: All participants (n = 11) completed all three trials. Change in Q̇ from baseline to hypoxia was not different between treatments. Change in PASP was significantly lower with the AZ (8.0 ± 0.7 mmHg) and MZ (9.0 ± 0.9 mmHg) treatments compared to placebo (PASP: 14.1 ± 1.3 mmHgP < 0.05). Change in PAO₂ was also decreased with both drug treatments (AZ: 54.8 ± 1.3 mmHg; MZ: 53.9 ± 1.3 mmHg) compared to placebo (48.5 ± 1.6 mmHg; P < 0.05). Conclusion: MZ attenuated HPV to the same degree as AZ. MZ also resulted in a similar improvement in PAO₂ as AZ during hypoxia compared to placebo. Trial Registration: This study was registered with the U.S. National Institutes of Health: NCT02760121 Funding: This project was funded by the Canadian Foundation for Innovation and by the Natural Science and Engineering Council of Canada.

Text

2017-08-08

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/62522

Interdisciplinary Studies

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/