CO liberated from a carbon monoxide-releasing molecule exerts a positive inotropic effect in doxorubicin-induced cardiomyopathy

Journal of Cardiovascular Pharmacology
M D MusamehB J Fuller

Abstract

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 microg/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 microM 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), su...Continue Reading

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Citations

Dec 23, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·T I AyudhyaN N Dingra
Dec 4, 2013·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Tran H TranRobert A Mangione
Dec 11, 2019·Medicinal Research Reviews·Xiaoxiao YangBinghe Wang

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