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Early effects of acetazolamide on hemoglobin mass and plasma volume in chronic mountain sickness at 5100 m.

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Title: Early effects of acetazolamide on hemoglobin mass and plasma volume in chronic mountain sickness at 5100 m.
Authors: Champigneulle B; Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38000 Grenoble, France., Stauffer E; Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team 'Vascular Biology and Red Blood Cell', Université Claude Bernard Lyon 1, Université de Lyon, France.; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.; Exploration Fonctionnelle Respiratoire, Médecine du Sport et de l'Activité Physique, Hospices Civils de Lyon, Hôpital Croix Rousse, Lyon, France., Robach P; Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38000 Grenoble, France.; National School for Mountain Sports, Site of the National School for Skiing and Mountaineering (ENSA), Chamonix, France., Doutreleau S; Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38000 Grenoble, France., Howe CA; Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia - Okanagan, Kelowna, Canada., Pina A; Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, IRCCS, S. Luca Hospital, Milan, Italy., Salazar-Granara AA; Universidad de San Martin de Porres, School of Medicine, Research Centre in Altitude Medicine, Lima, Peru., Hancco I; Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38000 Grenoble, France., Guergour D; Unité Biochimie Immunoanalyse, Service de Biochimie Biologie Moléculaire et Toxicologie Environnementale, Institut de Biologie et Pathologie, CHU Grenoble Alpes, France., Brugniaux JV; Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38000 Grenoble, France., Connes P; Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team 'Vascular Biology and Red Blood Cell', Université Claude Bernard Lyon 1, Université de Lyon, France.; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France., Pichon A; Laboratoire Move EA 6314, Faculté des Sciences du Sport, Universit. De Poitiers, Poitiers, France., Verges S; Univ. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, 38000 Grenoble, France.
Source: Pulmonology [Pulmonology] 2025 Dec 31; Vol. 31 (1), pp. 2416794. Date of Electronic Publication: 2024 Oct 24.
Publication Type: Journal Article; Randomized Controlled Trial
Language: English
Journal Info: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101723786 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2531-0437 (Electronic) Linking ISSN: 25310429 NLM ISO Abbreviation: Pulmonology Subsets: MEDLINE
Imprint Name(s): Publication: 2025- : [Philadelphia, PA] : Taylor & Francis
Original Publication: [Barcelona] : Elsevier España, [2018]-
MeSH Terms: Altitude Sickness*/drug therapy , Altitude Sickness*/blood , Altitude Sickness*/physiopathology , Acetazolamide*/therapeutic use , Acetazolamide*/administration & dosage , Acetazolamide*/pharmacology , Plasma Volume*/drug effects , Hemoglobins*/analysis , Hemoglobins*/drug effects , Hemoglobins*/metabolism , Carbonic Anhydrase Inhibitors*/therapeutic use, Humans ; Male ; Middle Aged ; Hematocrit ; Double-Blind Method ; Atorvastatin/therapeutic use ; Atorvastatin/administration & dosage ; Adult ; Chronic Disease ; Peru ; Altitude ; Treatment Outcome
Abstract: Introduction and Objectives: Chronic Mountain Sickness (CMS) syndrome, combining excessive erythrocytosis and clinical symptoms in highlanders, remains a public health concern in high-altitude areas, especially in the Andes, with limited therapeutic approaches. The objectives of this study were to assess in CMS-highlanders permanently living in La Rinconada (5100-5300 m, Peru, the highest city in the world), the early efficacy of acetazolamide (ACZ) and atorvastatin to reduce hematocrit (Hct), as well as the underlying mechanisms focusing on intravascular volumes.
Materials and Methods: Forty-one males (46±8 years of age) permanently living in La Rinconada for 15 [10-20] years and suffering from CMS were randomized between ACZ (250 mg once-daily; N  = 13), atorvastatin (20 mg once-daily; N  = 14) or placebo ( N  = 14) uptake in a double-blinded parallel study. Hematocrit (primary endpoint) as well as arterial blood gasses, total hemoglobin mass (Hb mass ) and intravascular volumes were assessed at baseline and after a mean (±SD) treatment duration of 19±2 days.
Results: ACZ increased PaO 2 by +13.4% (95% CI: 4.3 to 22.5%) and decreased Hct by -5.2% (95% CI: -8.3 to -2.2%), whereas Hct remained unchanged with placebo or atorvastatin. ACZ tended to decrease Hb mass (-2.6%, 95% CI: -5.7 to 0.5%), decreased total red blood cell volume (RBCV, -5.3%, 95% CI: -10.3 to -0.3%) and increased plasma volume (PV, +17.6%, 95% CI: 4.9 to 30.3%). Atorvastatin had no effect on intravascular volumes, while Hb mass and RBCV increased in the placebo group (+6.1%, 95% CI: 4.2 to 7.9% and +7.0%, 95%CI: 2.7 to 11.4%, respectively).
Conclusions: Short-term ACZ uptake was effective to reduce Hct in CMS-highlanders living at extreme altitude >5,000 m and was associated with both an increase in PV and a reduction in RBCV.
Contributed Indexing: Keywords: Acetazolamide; Chronic mountain sickness; Excessive erythrocytosis; Plasma volume; Total hemoglobin mass
Substance Nomenclature: O3FX965V0I (Acetazolamide)
0 (Hemoglobins)
A0JWA85V8F (Atorvastatin)
0 (Carbonic Anhydrase Inhibitors)
Entry Date(s): Date Created: 20230601 Date Completed: 20250130 Latest Revision: 20250424
Update Code: 20250425
DOI: 10.1016/j.pulmoe.2023.05.006
PMID: 37263861
Database: MEDLINE
Description
Abstract:Introduction and Objectives: Chronic Mountain Sickness (CMS) syndrome, combining excessive erythrocytosis and clinical symptoms in highlanders, remains a public health concern in high-altitude areas, especially in the Andes, with limited therapeutic approaches. The objectives of this study were to assess in CMS-highlanders permanently living in La Rinconada (5100-5300 m, Peru, the highest city in the world), the early efficacy of acetazolamide (ACZ) and atorvastatin to reduce hematocrit (Hct), as well as the underlying mechanisms focusing on intravascular volumes.<br />Materials and Methods: Forty-one males (46±8 years of age) permanently living in La Rinconada for 15 [10-20] years and suffering from CMS were randomized between ACZ (250 mg once-daily; N  = 13), atorvastatin (20 mg once-daily; N  = 14) or placebo ( N  = 14) uptake in a double-blinded parallel study. Hematocrit (primary endpoint) as well as arterial blood gasses, total hemoglobin mass (Hb <subscript>mass</subscript> ) and intravascular volumes were assessed at baseline and after a mean (±SD) treatment duration of 19±2 days.<br />Results: ACZ increased PaO <subscript>2</subscript> by +13.4% (95% CI: 4.3 to 22.5%) and decreased Hct by -5.2% (95% CI: -8.3 to -2.2%), whereas Hct remained unchanged with placebo or atorvastatin. ACZ tended to decrease Hb <subscript>mass</subscript> (-2.6%, 95% CI: -5.7 to 0.5%), decreased total red blood cell volume (RBCV, -5.3%, 95% CI: -10.3 to -0.3%) and increased plasma volume (PV, +17.6%, 95% CI: 4.9 to 30.3%). Atorvastatin had no effect on intravascular volumes, while Hb <subscript>mass</subscript> and RBCV increased in the placebo group (+6.1%, 95% CI: 4.2 to 7.9% and +7.0%, 95%CI: 2.7 to 11.4%, respectively).<br />Conclusions: Short-term ACZ uptake was effective to reduce Hct in CMS-highlanders living at extreme altitude &gt;5,000 m and was associated with both an increase in PV and a reduction in RBCV.
ISSN:2531-0437
DOI:10.1016/j.pulmoe.2023.05.006