title: Acetazolamide and chronic hypoxia: effects on haemorheology and pulmonary haemodynamics.
abstract: We tested the effect of acetazolamide on blood mechanical properties and pulmonary vascular resistance (PVR) during chronic hypoxia. Six groups of rats were either treated or not treated with acetazolamide (curative: treated after 10 days of hypoxic exposure; preventive: treated before hypoxic exposure with 40 mg · kg(-1) · day(-1)) and either exposed or not exposed to 3 weeks of hypoxia (at altitude >5,500 m). They were then used to assess the role of acetazolamide on pulmonary artery pressure, cardiac output, blood volume, haematological and haemorheological parameters. Chronic hypoxia increased haematocrit, blood viscosity and PVR, and decreased cardiac output. Acetazolamide treatment in hypoxic rats decreased haematocrit (curative by -10% and preventive by -11%), PVR (curative by -36% and preventive by -49%) and right ventricular hypertrophy (preventive -20%), and increased cardiac output (curative by +60% and preventive by +115%). Blood viscosity was significantly decreased after curative acetazolamide treatment (-16%) and was correlated with PVR (r=0.87, p<0.05), suggesting that blood viscosity could influence pulmonary haemodynamics. The fall in pulmonary vascular hindrance (curative by -27% and preventive by -45%) after treatment suggests that acetazolamide could decrease pulmonary vessels remodelling under chronic hypoxia. The effect of acetazolamide is multifactorial by acting on erythropoiesis, pulmonary circulation, haemorheological properties and cardiac output, and could represent a pertinent treatment of chronic mountain sickness.
authors.affiliation: Sorbonne Paris Cité, Gr-Ex, Laboratoire Réponses Cellulaires et Fonctionnelles à l'Hypoxie EA 2363, Bobigny, France. aurelion.pichon@orange.fr
authors.forename: Aurélien
authors.initials: A
authors.lastname: Pichon
authors.forename: Philippe
authors.initials: P
authors.lastname: Connes
authors.forename: Patricia
authors.initials: P
authors.lastname: Quidu
authors.forename: Dominique
authors.initials: D
authors.lastname: Marchant
authors.forename: Julien
authors.initials: J
authors.lastname: Brunet
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Levy
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Innocent
authors.initials: I
authors.lastname: Safeukui
authors.forename: Florence
authors.initials: F
authors.lastname: Cymbalista
authors.forename: Maxime
authors.initials: M
authors.lastname: Maignan
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Richalet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Favret
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000532:Altitude Sickness / Q000628:therapy; D000818:Animals; D001809:Blood Viscosity; D001810:Blood Volume; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002908:Chronic Disease; D006321:Heart / Q000502:physiology; D006400:Hematocrit; D006439:Hemodynamics; D018056:Hemorheology; D006863:Hydrogen-Ion Concentration; D006976:Hypertension, Pulmonary / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide