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dc.contributor.authorHole, Lisa Drangeen_US
dc.contributor.authorLarsen, Terje H.en_US
dc.contributor.authorFossan, Kjell Oveen_US
dc.contributor.authorLimé, Fredriken_US
dc.contributor.authorSchjøtt, Janen_US
dc.date.accessioned2015-03-19T12:21:53Z
dc.date.available2015-03-19T12:21:53Z
dc.date.issued2014-09eng
dc.identifier.issn1530-7905
dc.identifier.urihttps://hdl.handle.net/1956/9590
dc.description.abstractInterventions to reduce the cardiotoxicity of doxorubicin are clinically relevant. Pharmacological preconditioning mimicking ischemic preconditioning has been demonstrated with morphine and represents an acceptable clinical intervention. The purpose of this study was to examine if pretreatment in vivo with morphine could reduce doxorubicin-induced cardiotoxicity ex vivo in a rat model. Wistar rats were divided into six groups and pretreated with an intraperitoneal (i.p.) injection of 3 or 10 mg/kg morphine, 1 mg/kg naloxone and saline, 1 mg/ kg naloxone and 3 mg/kg morphine or saline, 60 min before excision of the heart. Biochemical indices such as troponin T (TnT) and hydrogen peroxide (H2O2) in effluate were measured together with physiological parameters in Langendorff hearts before and after doxorubicin infusion (2 mg/mL 0.05 mL/min for 45 min). Myocardial content of doxorubicin was measured at the end of infusion. Pretreatment with morphine, irrespective of dosage, produced a significant loss in left ventricular-developed pressure and an increase of TnT and H2O2 in effluate before doxorubicin infusion (p < 0.05). Morphine also produced a significant increase in left ventricular end-diastolic pressure and an increase of TnT and H2O2 in effluate (p < 0.05) at the end of doxorubicin infusion. Naloxone, a non-selective opioid receptor antagonist, abolished the effects of morphine both before and after doxorubicin infusion. Morphine, irrespective of dosage, increased myocardial content of doxorubicin compared to pretreatment with saline (p < 0.05). Pretreatment with morphine is associated with a cardiodepressive effect and enhances cardiotoxicity of doxorubicin measured by increased myocardial accumulation of doxorubicin and physiological and biochemical indices. The negative effects observed in our rat model are abolished by naloxone.en_US
dc.language.isoengeng
dc.publisherSpringereng
dc.relation.ispartof<a href="http://hdl.handle.net/1956/9591" target="blank">Cardiotoxicity of Doxorubicin. A Study of Methods and Protective Interventions in Rat Models</a>eng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/eng
dc.subjectDoxorubicineng
dc.subjecthigh-sensitivity cardiac troponin Teng
dc.subjectHydrogenperoxideeng
dc.subjectHearteng
dc.subjectDoxorubicinoleng
dc.subjectCardiotoxicityeng
dc.titleMorphine enhances doxorubicin-induced cardiotoxicity in the raten_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2015-03-04T12:43:59Zen_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright The Author(s) 2014
dc.identifier.doihttps://doi.org/10.1007/s12012-014-9249-z
dc.identifier.cristin1115973
dc.source.journalCardiovascular Toxicology
dc.source.4014
dc.source.143
dc.source.pagenumber251-259
dc.subject.nsiVDP::Medical sciences: 700::Clinical medical sciences: 750::Cardiology: 771eng
dc.subject.nsiVDP::Medical sciences: 700::Basic medical, dental and veterinary sciences: 710::Clinical pharmacology: 739eng
dc.subject.nsiVDP::Medisinske fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771nob
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Klinisk farmakologi: 739nob


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Except where otherwise noted, this item's license is described as Attribution CC BY