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Effects of Acetazolamide on Ventilatory, Cerebrovascular, and Pulmonary Vascular Responses to Hypoxia

Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands; School of Sport and Exercise Sciences, University of Birmingham, Birmingham, United Kingdom; and Departments of Physiology and Biophysics, Medicine, and Clinical Neurosciences, Faculty of Medicine, and Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada

Correspondence and requests for reprints should be addressed to Marc J. Poulin, Ph.D., D.Phil., Departments of Physiology and Biophysics, and Clinical Neurosciences, Faculty of Medicine and Faculty of Kinesiology, University of Calgary, Calgary, AB, T2N 4N1 Canada. E-mail: poulin{at}ucalgary.ca

Rationale: Acute mountain sickness (AMS) may affect individuals who (rapidly) ascend to altitudes higher than 2,000–3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema, a hydrostatic edema associated with increased pulmonary capillary pressures. Acetazolamide is effective against AMS, possibly by increasing ventilation and cerebral blood flow (CBF). In animals, it inhibits hypoxic pulmonary vasoconstriction.

Objectives: We examined the influence of acetazolamide on the response to hypoxia of ventilation, CBF, and pulmonary vascular resistance (PVR).

Methods: In this double-blind, placebo-controlled, randomized study, nine subjects ingested 250 mg acetazolamide every 8 h for 3 d. On the fourth test day, we measured the responses of ventilation, PVR, and CBF to acute isocapnic hypoxia (20 min) and sustained poikilocapnic hypoxia (4 h). Ventilation was measured with pneumotachography. Hypoxia was achieved with dynamic end-tidal forcing. The maximum pressure difference across the tricuspid valve (Pmax, a good index of PVR) was measured with Doppler echocardiography. CBF was measured by transcranial Doppler ultrasound.

Results: In normoxia, acetazolamide increased ventilation and reduced Pmax, but did not influence CBF. The ventilatory and CBF responses to acute isocapnic hypoxia were unaltered, but the rise in Pmax was reduced by 57%. The increase in Pmax by sustained poikilocapnic hypoxia observed after placebo was reduced by 34% after acetazolamide, the ventilatory response was increased, but the CBF response remained unaltered.

Conclusions: Acetazolamide has complex effects on ventilation, PVR, and CBF that converge to optimize brain oxygenation and may be a valuable means to prevent/treat high-altitude pulmonary edema.

Key Words: pulmonary resistance • cerebral blood flow • altitude sickness • hypoxic responses • mountaineering

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Acetazolamide is effective against acute mountain sickness, but the mechanisms for this effect are not completely characterized. What This Study Adds to the Field Acetazolamide has benefit in alleviating acute and subacute hypoxia-induced pulmonary vasoconstriction and increased pulmonary artery pressures.

 

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