Protective Effects of Ranolazine, a Novel Anti-ischemic Drug, on the Hydrogen Peroxide-Induced Derangements in Isolated, Per fused Rat Heart: Comparison With Dichloroacetate

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Author(s)

Abstract

The effect of ranolazine, a novel anti-ischemic drug that stimulates the activity of pyruvate dehydrogenase, on hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>)-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. H<SUB>2</SUB>O<SUB>2</SUB> (600 μM) 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 H<SUB>2</SUB>O<SUB>2</SUB> were significantly attenuated by ranolazine (10 or 20 μM). On the other hand, DCA (1 mM) was ineffective in attenuating the H<SUB>2</SUB>O<SUB>2</SUB>-induced mechanical and metabolic derangements. Ranolazine, however, did not modify the tissue MDA level, which was increased by H<SUB>2</SUB>O<SUB>2</SUB>. In the normal (H<SUB>2</SUB>O<SUB>2</SUB>-untreated) heart, ranolazine did not alter the mechanical function and energy metabolism. These results demonstrate that ranolazine attenuates mechanical and metabolic derangements induced by H<SUB>2</SUB>O<SUB>2</SUB>. It is suggested that the protective action of ranolazine against the H<SUB>2</SUB>O<SUB>2</SUB>-induced derangements is due to neither the energy-sparing, DCA-like, nor anti-oxidant effects.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 77(1), 31-39, 1998-05-01

    The Japanese Pharmacological Society

References:  30

Codes

  • NII Article ID (NAID)
    10008680082
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4503672
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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