Document Detail


Depletion of lactate by dichloroacetate reduces cardiac efficiency after hemorrhagic shock.
MedLine Citation:
PMID:  10947168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 x mm Hg/mL/100 g tissue). During resuscitation by DCA, myocardial lactate consumption was reduced (21.4 +/- 3.7 vs. 70.7 +/- 16.3 micromole/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.
Authors:
R W Barbee; J A Kline; J A Watts
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  14     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-11-21     Completed Date:  2001-01-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  208-14     Citation Subset:  IM    
Affiliation:
Emergency Medicine Research, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
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MeSH Terms
Descriptor/Qualifier:
Acidosis, Lactic / etiology,  physiopathology*
Animals
Dichloroacetate / pharmacology,  therapeutic use,  toxicity*
Dogs
Drug Evaluation, Preclinical
Energy Metabolism / drug effects*
Enzyme Activation / drug effects
Fatty Acids / metabolism
Fluid Therapy / adverse effects
Hemodynamics / drug effects*
Isotonic Solutions / therapeutic use
Lactic Acid / metabolism*,  toxicity
Myocardium / metabolism*
Pyruvate Dehydrogenase Complex / metabolism
Resuscitation
Shock, Hemorrhagic / blood,  complications,  physiopathology*
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Isotonic Solutions; 0/Pyruvate Dehydrogenase Complex; 13425-80-4/Dichloroacetate; 50-21-5/Lactic Acid; 8022-63-7/Ringer's lactate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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