Document Detail

Digitalis toxicity during acute hypoxia in intact conscious dogs.
MedLine Citation:
PMID:  239218     Owner:  NLM     Status:  MEDLINE    
Intact, conscious dogs were studied under normal and hypobaric conditions to assess the influence of acute hypoxia on the ability of the animals to tolerate ouabain. Animals were made acutely hypoxic by exposure to hypobaric conditions in a chamber maintained at 446 mm Hg. The ability of the dogs to tolerate ouabain was determined by administering intravenously 7.5 mug/kg of the drug as a loading dose followed by infusion at a rate of 3.0 mug/kg/min to an end point consisting of the development of ventricular or atrioventricular junctional tachycardia. Eight dogs, each acting as its own control, were studied under normoxic and acutely hypoxic conditions. During hypoxia, mean arteriol pO2 decreased to 39 plus or minus 1 (S.E.) mm Hg from 80 plus or minus 1 mm Hg at sea level (P less than .001). The cumulative toxic dose of ouabain was modestly but significantly less (P less than .05) during acute hypoxia (71.7 plus or minus 4.3 mug/kg) compared with normoxic (79.2 plus or minus 4.1 mug/kg) conditions. In these experiments a marked hyperventilation response to ouabain was observed just before onset of toxicity which resulted in a pronounced rise in mean arterial pH (normoxia: 7.39 plus or minus 0.01 to 7.72 plus or minus 0.01; hypoxia: 7.48 plus or minus 0.01 to 7.71 plus or minus 0.04) and fall in pCO2 (normoxia: 41 plus or minus 1 to 14 plus or minus 1 mm Hg; hopoxia: 34 plus or minus 1 to 16 plus or minus 2 mm Hg). Ouabain-induced increases in systemic arterial pressure were comparable in normal and acutely hypoxic animals. Thus, acute hypoxia in unanesthetized dogs exposed to hypobaric conditions results in a decrease of only 10% in the ouabain dose required to produce cardiac arrhythmias, and toxic doses of ouabain produce a striking respiratory alkalosis.
G A Beller; T W Smith
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  193     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1975 Jun 
Date Detail:
Created Date:  1975-11-01     Completed Date:  1975-11-01     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  963-8     Citation Subset:  IM    
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MeSH Terms
Anoxia / physiopathology*
Arrhythmias, Cardiac / chemically induced
Atmospheric Pressure
Blood Pressure / drug effects
Carbon Dioxide / blood
Heart Rate / drug effects
Hydrogen-Ion Concentration
Ouabain / toxicity*
Oxygen / blood
Respiration / drug effects
Reg. No./Substance:
124-38-9/Carbon Dioxide; 630-60-4/Ouabain; 7782-44-7/Oxygen

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

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