| Dichloroacetate reduces diaphragmatic lactate formation but impairs respiratory performance. | |
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MedLine Citation:
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PMID: 11719308 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 H(2)O/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. |
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Authors:
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R Ciufo; A Dimarco; D Stofan; D Nethery; G Supinski |
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Publication Detail:
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Type: Evaluation Studies; In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 164 ISSN: 1073-449X ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2001 Nov |
Date Detail:
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Created Date: 2001-11-23 Completed Date: 2002-06-19 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1669-74 Citation Subset: AIM; IM |
Affiliation:
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Pulmonary Division, Department of Medicine, Case Western Reserve University and MetroHealth Medical Center, Cleveland, Ohio, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Airway Resistance Analysis of Variance Animals Dichloroacetate / pharmacology* Lactic Acid / metabolism* Male Muscle Contraction / drug effects Rats Rats, Inbred Strains Respiratory Insufficiency / metabolism Respiratory Mechanics / drug effects* Respiratory Muscles / drug effects*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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38926//PHS HHS; 54825//PHS HHS |
| Chemical | |
Reg. No./Substance:
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13425-80-4/Dichloroacetate; 50-21-5/Lactic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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