Dichloroacetate reduces diaphragmatic lactate formation but impairs respiratory performance

Russ Ciufo, Anthony Dimarco, Daniel Stofan, David Nethery, Gerald Supinski

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Previous studies have found that administration of dichloroacetate (DCA), an agent that reduces lactic acid generation, increases limb muscle endurance. The purpose of the present study was to determine if this agent also improves respiratory muscle performance. To examine this issue, we determined the effect of DCA administration on the response to application of a large inspiratory resistive load (32,000 cm H2O/L/s) in unanesthetized decerebrate rats. Studies were carried out in four groups of animals: saline unloaded, DCA unloaded, saline loaded, and DCA loaded. DCA was administered as 100 mg/kg, given intravenously over 30 min, prior to respiratory loading. We found that diaphragm lactate levels were higher in saline-treated loaded animals than in unloaded controls and that DCA administration prevented loading-induced increases in diaphragm lactate (p < 0.001). DCA-treated animals tolerated loading poorly, however, with a more rapid reduction in diaphragm pressure generation and a shorter time to respiratory arrest (42 ± 3 min) than for saline-treated animals (57 ± 3 min, p < 0.01). These data indicate that DCA administration decreases the tolerance to loaded breathing despite reductions in diaphragm lactate concentrations. We speculate that suppression of lactate formation by DCA may impair metabolic regulation within the diaphragm during resistive loaded breathing.

Original languageEnglish
Pages (from-to)1669-1674
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number9
StatePublished - Nov 1 2001


  • Diaphragm
  • Lactate
  • Respiratory failure
  • Respiratory muscles

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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