title: Doxorubicin toxicity in perfused rat heart. Decreased cell death at low oxygen tension.
abstract: The purpose of these studies was to test whether O2 tension influences cardiotoxicity due to doxorubicin. Isolated hearts were perfused by the method of Langendorff at constant pressure with Krebs-Henseleit buffer saturated with 5% CO2 and either 95% or 20% O2. Toxicity due to doxorubicin was evaluated from changes in heart rate and from uptake of trypan blue by nonviable nuclei. Heart rate was stable in control hearts perfused at 95% O2 for 30 minutes but decreased in hearts perfused at 20% O2. Doxorubicin (30 microM) increased O2 uptake due to redox cycling by approximately 75 mumol/g/hr at 95% O2 but had no effect in hearts perfused at 20% O2. Heart rate decreased during 30 minutes of perfusion with doxorubicin and 95% or 20% O2, with greater decreases occurring with 95% than 20% O2 compared with values for the respective untreated controls. Irreversible cell damage indexed from uptake of vital dye due to doxorubicin was threefold greater than control at 95% O2 but was not different from control at at 20% O2. These data are consistent with the hypothesis that O2 tension is an important determinant of toxicity due to doxorubicin.
authors.affiliation: Laboratory of Hepatobiology and Toxicology, University of North Carolina, Chapel Hill 27599-7365.
authors.forename: P E
authors.initials: PE
authors.lastname: Ganey
authors.forename: L S
authors.initials: LS
authors.lastname: Carter
authors.forename: R A
authors.initials: RA
authors.lastname: Mueller
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D000818:Animals; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006324:Heart Arrest, Induced; D009206:Myocardium / Q000473:pathology; D009994:Osmolar Concentration; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011189:Potassium Chloride; D051381:Rats
chemical_list: D011189:Potassium Chloride; D004317:Doxorubicin