Attenuation of human hypoxic pulmonary vasoconstriction by acetazolamide and methazolamide

Journal of Applied Physiology
Lindsey M BouletGlen E Foster

Abstract

Acetazolamide, a carbonic anhydrase inhibitor used for preventing altitude illness attenuates hypoxic pulmonary vasoconstriction (HPV) while improving oxygenation. Methazolamide, an analog of acetazolamide, is more lipophilic, has a longer half-life, and activates a major antioxidant transcription factor. However, its influence on the hypoxic pulmonary response in humans is unknown. To determine if a clinically relevant dosing of methazolamide improves oxygenation, attenuates HPV and augments plasma antioxidant capacity in men exposed to hypoxia when compared to an established dosing of acetazolamide known to suppress HPV. In this double-blind, placebo-controlled, cross-over trial, eleven participants were randomized to treatments with methazolamide (100mg b.i.d.) and acetazolamide (250mg t.i.d.) for two days prior to 60 minutes of hypoxia (FIO2≈0.12). Pulmonary artery systolic pressure (PASP), alveolar ventilation (V̇A), blood gases and markers of redox status were measured. Pulmonary vascular sensitivity to hypoxia was determined by indexing PASP to alveolar PO2. Acetazolamide caused greater metabolic acidosis compared with methazolamide, but the augmented V̇A and improved oxygenation with hypoxia were similar. The rise in PA...Continue Reading

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Methods Mentioned

BETA
MDA

Clinical Trials Mentioned

NCT02760121

Software Mentioned

R Foundation for Statistical Computing
EchoPAC
LabChart
R

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