Document Detail


Fatty acids antagonize bupivacaine - induced I(Na) blockade.
MedLine Citation:
PMID:  21970771     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Theories regarding the mechanism of intravenous fat emulsion for bupivacaine cardiotoxicity include creation of an intravascular lipid sink into which the cardiotoxic drug is sequestered, an improvement of impaired cardiac metabolism, and restoration of cardiomyocyte function by increasing intracellular calcium. However, work in this area is inconclusive and a more mechanistic explanation is desirable. We used a heterologous expression system (HEK-293 cells) and voltage clamp techniques to study the electrophysiologic effects of bupivacaine, polyunsaturated, and saturated fatty acids on sodium current (I(Na)) in stable cell lines expressing human cardiac sodium channels. Linolenic (polyunsaturated) and stearic (saturated) fatty acids were selected for study as they are components of commonly used lipid infusions. Bupivacaine - induced significant tonic and use dependent I(Na) block, as expected. Linolenic and stearic fatty acids directly modulated I(Na), inducing primarily tonic block. Greater block was seen with linolenic acid as compared with stearic acid. Simultaneous exposure to bupivacaine and fatty acids reduced both the tonic and use dependent block compared with bupivacaine alone. Reduction of bupivacaine - induced I(Na) block was greatest in cells treated with linolenic acid. These results suggest that the salutary effects of intravenous fat emulsion may be, in part, due to a direct modulatory effect of fatty acids on cardiac sodium channels.
Authors:
Allan R Mottram; Carmen R Valdivia; Jonathan C Makielski
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical toxicology (Philadelphia, Pa.)     Volume:  49     ISSN:  1556-9519     ISO Abbreviation:  Clin Toxicol (Phila)     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101241654     Medline TA:  Clin Toxicol (Phila)     Country:  England    
Other Details:
Languages:  eng     Pagination:  729-33     Citation Subset:  AIM; IM    
Affiliation:
University of Wisconsin, Division of Emergency Medicine , 600 Highland Ave, F2/204 CSC, MC 3280, Madison , United States.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Earlier recognition of nephrotoxicity using novel biomarkers of acute kidney injury.
Next Document:  Prognostic significance of arterial blood gas analysis in the early evaluation of Paraquat poisoning...