Format

Send to

Choose Destination
Jpn J Pharmacol. 1998 May;77(1):31-9.

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

Author information

1
Department of Pharmacology, Asahikawa Medical College, Japan.

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 metabolic derangements induced by H2O2. It is suggested that the protective action of ranolazine against the H2O2-induced derangements is due to neither the energy-sparing, DCA-like, nor anti-oxidant effects.

PMID:
9639058
DOI:
10.1254/jjp.77.31
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic
Loading ...
Support Center