Depletion of lactate by dichloroacetate reduces cardiac efficiency after hemorrhagic shock

R. Wayne Barbee, Jeffrey A. Kline, John A. Watts

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

We have demonstrated previously that dichloroacetate (DCA) treatment in rodents ameliorates, via activation of the pyruvate dehydrogenase complex, the cardiovascular depression observed after hemorrhagic shock. To explore the mechanism of this effect, we administered DCA in a large animal model of hemorrhagic shock. Mongrel hounds were anesthetized with 1.5 % isoflurane and were measured for hemodynamics, myocardial contractility, and myocardial substrate utilization. They were hemorrhaged to a mean arterial pressure of 35 mm Hg for 90 min or until arterial lactate levels reached 7.0 mM (1137 ± 47 mL or 49 ± 2 % total blood volume). Animals were chosen at random to receive DCA dissolved in water or an equal volume of saline at the onset of resuscitation. Two-thirds of the shed blood volume was returned immediately after giving an equivalent volume of saline. Two hours after the onset of resuscitation, mean arterial pressure was not different between DCA and control groups (79 ± 3 vs. 82 ± 3 mm Hg, respectively). Arterial lactate levels were significantly reduced by DCA (0.5 ± 0.06 vs. 2.0 ± 0.2 mM). However, DCA treatment was associated with a decreased stroke volume index (0.56 ± 0.06 vs. 0.82 ± 0.08 mL/kg/beat) and a decreased myocardial efficiency (19 vs. 41 L* mm Hg/mL/100 g tissue). During resuscitation by DCA, myocardial lactate consumption was reduced (21.4 ± 3.7 vs. 70.7 ± 16.3 μmole/min/100 g tissue) despite a three-fold increase in myocardial pyruvate dehydrogenase activity, while free fatty acid levels actually began to rise. Although increased lactate oxidation should be beneficial during resuscitation, we propose that DCA treatment led to a deprivation of myocardial lactate supply, which reduced net myocardial lactate oxidation, thus compromising myocardial function during resuscitation from hemorrhagic shock.

Original languageEnglish (US)
Pages (from-to)208-214
Number of pages7
JournalShock
Volume14
Issue number2
DOIs
StatePublished - Aug 2000

Keywords

  • Anesthesia
  • Autologous blood transfusion
  • Crystalloid
  • Emergency medicine
  • Hemodynamics
  • Hypovolemia management
  • Lactic acid
  • Left ventricular function
  • Nonesterified fatty acids
  • Pyruvate dehydrogenase complex

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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