Document Detail


Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis.
MedLine Citation:
PMID:  19880504     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we investigated possible separate effects of H+ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic - normoxic) ventilation over (hypoxic - normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic - normoxic) ventilation over (logPa(O2) hypoxia - logPa(O2) normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal Po2 to approximately 50 Torr lasting 5 min each at three different constant end-tidal Pco2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa(CO2), and a parallel leftward shift of the ventilatory CO2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arterial [H+] ([H+](a)) to higher values of [H+](a) without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H+ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H+](a) response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated.
Authors:
Luc J Teppema; Eveline L A van Dorp; Albert Dahan
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial     Date:  2009-10-30
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  298     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-18     Completed Date:  2010-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L89-95     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Leiden University Medical Center, PO Box 9600 2300 RC, Leiden, The Netherlands. l.j.s.m.teppema@lumc.nl
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MeSH Terms
Descriptor/Qualifier:
Acetazolamide / adverse effects*
Acidosis, Respiratory / chemically induced*,  complications,  physiopathology*
Anoxia / complications,  physiopathology*
Bicarbonates / administration & dosage,  pharmacology
Carbon Dioxide / metabolism
Female
Humans
Hyperoxia / complications,  physiopathology
Infusions, Intravenous
Male
Placebos
Protons*
Pulmonary Artery / drug effects,  physiopathology*
Pulmonary Ventilation / drug effects,  physiology*
Respiratory Hypersensitivity / complications,  physiopathology
Rest
Young Adult
Chemical
Reg. No./Substance:
0/Bicarbonates; 0/Placebos; 0/Protons; 124-38-9/Carbon Dioxide; 59-66-5/Acetazolamide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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