Published ahead of print on August 26, 2005, doi:10.1164/rccm.200505-807OC Am. J. Respir. Crit. Care Med., Volume 172, Number 11, December 2005, 1427-1433 A more recent version of this article appeared on December 1, 2005
Submitted on May 23, 2005 Acetazolamide, a Treatment for Chronic Mountain SicknessJean-Paul Richalet1*,1 Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie, Universite Paris 13, Bobigny, France; Service de Physiologie et Explorations Fonctionnelles, Hopital Avicenne, AP-HP, Bobigny, France, 2 Laboratorio de Transporte de Oxigeno, Universidad Peruana Cayetano Heredia, Lima, Peru, 3 Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie, Universite Paris 13, Bobigny, France; Unite 280, INSERM, Lyon, France, 4 Service de Physiologie et Explorations Fonctionnelles, Hopital Avicenne, AP-HP, Bobigny, France, 5 Service de Pharmacie, Hopital Avicenne, AP-HP, Bobigny, France, 6 Laboratoire Reponses cellulaires et fonctionnelles a l'hypoxie, Universite Paris 13, Bobigny, France, 7 Laboratoire National de depistage du dopage, Chatenay-Malabry, France, 8 Laboratoire de Biochimie, Hopital Henri Mondor, AP-HP, Creteil, France * To whom correspondence should be addressed. E-mail: richalet{at}smbh.univ-paris13.fr.
Rationale. Chronic mountain sickness or Monge's disease is characterized by an excessive polycythemia in high altitude dwellers, with a prevalence of 5 to 18 % above 3,200 m. To date, no pharmacological treatment is available. Objectives. We evaluated the efficacy of acetazolamide in the treatment of chronic mountain sickness and the importance of nocturnal hypoxemia in its pathophysiology. Methods. A double blind placebo-controlled study was performed in three groups of patients from Cerro de Pasco, Peru (4,300 m), treated orally for 3 weeks with placebo (n=10), 250 mg (n=10) and 500 mg (n=10) of acetazolamide, daily. Results. Acetazolamide decreased hematocrit by 7.1% (P<0.001) and 6.7% (P<0.001), serum erythropoietin by 67% (P<0.01) and 50% (P<0.001), serum soluble transferrin receptors by.11.1% (P<0.05) and.3.4% (P<0.001) and increased serum ferritin by 540% (P<0.001) and 134% (P<0.001) for 250 and 500 mg acetazolamide, respectively. Acetazolamide (250 mg) increased nocturnal arterial O2 saturation by 5% (P<0.01), decreased mean nocturnal heart rate by 11% (P<0.05) and the number of apnea/hypopnea during sleep by 74% (P<0.05). The decrease in erythropoietin was mainly attributed to the acetazolamide-induced increase in ventilation and arterial O2 saturation,. Conclusions. Acetazolamide is the first efficient pharmacological treatment of chronic mountain sickness without adverse effects, by reducing hypoventilation which may be accentuated during sleep and blunting erythropoiesis. Its low cost may allow a wide development with a considerable positive impact on public health in high altitude regions. Key words: hypoxia, altitude, nocturnal ventilation, erythropoietin, soluble transferrin receptors
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