title: Renal carbonic anhydrase inhibition reduces high altitude sleep periodic breathing.
abstract: The efficacy of carbonic anhydrase (CA) inhibitors in amelioration of periodic breathing during sleep at high altitude is not fully understood. Although CA is present in a number of tissues, we hypothesized that selective renal CA inhibition without physiologically important inhibition of other tissue CA, may be sufficient alone by its generation of a mild metabolic acidosis to stimulate ventilation and prevent periodic breathing. We studied benzolamide (3 mg/kg), a selective inhibitor of renal CA, in 4 climbers on ventilation and ventilatory responses at sea level and on arterial O2 saturation (SaO2%) and periodic breathing during sleep at altitude. At sea level, ventilation increased and PaO2 rose accompanied by a mild metabolic acidosis. The isocapnic hypoxic ventilatory response was unchanged but the hyperoxic hypercapnic ventilatory response rose 40%. At high altitude (4400 m), daytime SaO2% improved from 81 to 85 and venous plasma HCO3- fell from 18.9 to 14.8 mM. During sleep, mean SaO2% rose from 76 to 80 and periodic breathing decreased 75%. We conclude that metabolic acidosis occurring with all CA inhibitors is one of the major stimulant actions of these drugs on ventilation while awake and during sleep at high altitude.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: E R
authors.initials: ER
authors.lastname: Swenson
authors.forename: K L
authors.initials: KL
authors.lastname: Leatham
authors.forename: R C
authors.initials: RC
authors.lastname: Roach
authors.forename: R B
authors.initials: RB
authors.lastname: Schoene
authors.forename: W J
authors.initials: WJ
authors.lastname: Mills
authors.forename: P H
authors.initials: PH
authors.lastname: Hackett
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000503:physiopathology; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000188:drug therapy / Q000503:physiopathology; D001574:Benzolamide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D010507:Periodicity; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012119:Respiration / Q000187:drug effects* / Q000502:physiology; D012890:Sleep / Q000502:physiology
chemical_list: D001574:Benzolamide; D010100:Oxygen