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CO Liberated From a Carbon Monoxide-Releasing Molecule Exerts a Positive Inotropic Effect in Doxorubicin-Induced Cardiomyopathy

Musameh, D, Muntaser ; Green, J, Colin ; Mann, E, Brian ; Motterlini, J, Roberto ; Fuller, J, Barry

Journal of Cardiovascular Pharmacology, 2010, Vol.55(2), pp.168-175 [Rivista Peer Reviewed]

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  • Titolo:
    CO Liberated From a Carbon Monoxide-Releasing Molecule Exerts a Positive Inotropic Effect in Doxorubicin-Induced Cardiomyopathy
  • Autore: Musameh, D, Muntaser ; Green, J, Colin ; Mann, E, Brian ; Motterlini, J, Roberto ; Fuller, J, Barry
  • Note di contenuto: Carbon monoxide (CO) liberated by a water-soluble carbon monoxide-releasing molecule (CORM-3) induces a positive inotropic effect with a negative chronotropic effect in normal rat hearts. However, the efficacy of CORM-3 under conditions of chronic cardiac insufficiency is unknown. In a rat model of doxorubicin-induced cardiomyopathy, CORM-3 (20 μg/min) produced a positive inotropic effect as demonstrated by significant increases in systolic pressure (P < 0.05) and pressure derivative (dp/dt max) over time (P < 0.05). A similar dose of CO-depleted negative control (inactive CORM-3) failed to cause any change in these parameters. When the inotrope dobutamine was added at a dose of 10 μM following CORM-3, there was no additional increase in systolic pressure or dp/dt max. However, significant rises in systolic pressure and dp/dt max were observed after dobutamine administration to the hearts previously treated with inactive CORM-3. These results suggest that CORM-3 produces a positive inotropic effect in doxorubicin cardiomyopathy rat hearts, similar to that reported previously in normal hearts. The inotropic effect produced by CO in the doxorubicin cardiomyopathy heart was mimicked by a classical inotrope (dobutamine), suggesting that either a maximal inotropic effect is achieved at this dose of CORM-3 or both drugs utilize shared signaling pathways in cardiac muscle.
  • Fa parte di: Journal of Cardiovascular Pharmacology, 2010, Vol.55(2), pp.168-175
  • Soggetti: Carbon Monoxide -- Therapeutic Use ; Cardiomyopathies -- Chemically Induced ; Cardiotonic Agents -- Therapeutic Use ; Doxorubicin -- Toxicity ; Organometallic Compounds -- Therapeutic Use
  • Tipo: Articolo
  • Identificativo: ISSN: 0160-2446 ; DOI: 10.1097/FJC.0b013e3181ca4bbc

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