Protective effects of ranolazine, a novel anti-ischemic drug, on the hydrogen peroxide-induced derangements in isolated, perfused rat heart: comparison with dichloroacetate

Japanese Journal of Pharmacology
H MatsumuraY Abiko

Abstract

The effect of ranolazine, a novel anti-ischemic drug that stimulates the activity of pyruvate dehydrogenase, on hydrogen peroxide (H2O2)-induced mechanical and metabolic derangements was studied in isolated rat heart and compared with that of dichloroacetate (DCA), an activator of pyruvate dehydrogenase. The heart was perfused aerobically by the Langendorff's technique at a constant flow and driven electrically. H2O2 (600 microM) decreased the left ventricular developed pressure and increased the left ventricular end-diastolic pressure (i.e., mechanical dysfunction), decreased the tissue level of adenosine triphosphate (i.e., metabolic derangement), and increased the tissue level of malondialdehyde (MDA) (i.e., lipid peroxidation). These mechanical and metabolic derangements induced by H2O2 were significantly attenuated by ranolazine (10 or 20 microM). On the other hand, DCA (1 mM) was ineffective in attenuating the H2O2-induced mechanical and metabolic derangements. Ranolazine, however, did not modify the tissue MDA level, which was increased by H2O2. In the normal (H2O2-untreated) heart, ranolazine did not alter the mechanical function and energy metabolism. These results demonstrate that ranolazine attenuates mechanical and ...Continue Reading

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Citations

Nov 26, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Francesco CorradiRaffaele De Caterina
Feb 18, 2014·Cardiovascular Toxicology·Lisa Drange HoleJan Schjøtt
May 19, 2010·PloS One·Syamantak MajumderSuvro Chatterjee
Jan 22, 2013·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Nael Hawwa, Venu Menon
Aug 14, 2012·The American Journal of Cardiology·Rajesh VenkataramanAmi E Iskandrian
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Jul 3, 2013·The Journal of Pharmacology and Experimental Therapeutics·Giorgio Minotti
Apr 20, 2006·Drugs·M Asif A Siddiqui, Susan J Keam

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