Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart

Chen Barak, Mark K. Reed, Stephen P. Maniscalco, Dean Sherry, Craig R Malloy, Michael E Jessen

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The effects of dichloroacetate (DCA) on fatty acid oxidation and flux through pyruvate dehydrogenase (PDH) were studied in ischemic, reperfused myocardium supplied with glucose, long-chain fatty acids, lactate, pyruvate, and acetoacetate. The oxidation rates of all substrates were determined by combined 13C nuclear magnetic resonance (NMR) spectroscopy and oxygen- consumption measurements, and PDH flux was assessed by lactate plus pyruvate oxidation. In nonischemic control hearts, DCA increased PDH flux more than eightfold (from 0.68 ± 0.28 to 5.81 ± 1.16 μmol/min/g dry weight; n = 8 each group; p < 0.05) and significantly inhibited the oxidation of acetoacetate and fatty acids. DCA also improved mechanical recovery after 30 min of ischemia plus 30 min of reperfusion but did not significantly increase PDH flux measured at the end of the reperfusion period (1.35 ± 0.42 μmol/min/g dry weight) compared with untreated ischemic hearts (0.87 ± 0.28 μmol/min/g dry weight; n = 8 each group; p = NS). Although DCA had a modest effect on functional recovery in the reperfused myocardium, this beneficial effect was not associated with either marked stimulation of PDH flux or inhibition of fatty acid oxidation.

Original languageEnglish (US)
Pages (from-to)336-344
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume31
Issue number3
DOIs
StatePublished - Mar 1 1998

Keywords

  • C Nuclear magnetic resonance
  • Dichloroacetate
  • Ischemia
  • Myocardial metabolism

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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