Document Detail

Lasting alterations of the cardiac sodium current by short term hyperlipidemia as a mechanism for initiation of cardiac remodeling.
MedLine Citation:
PMID:  24240869     Owner:  NLM     Status:  Publisher    
Clinical and animal studies indicate that increased fatty acid delivery to lean tissues induce cardiac electrical remodeling and alterations of cellular calcium homeostasis. Since this may represent a mechanisms initiating cardiac dysfunction during establishment of insulin resistance and diabetes or anaerobic cardiac metabolism (ischemia), we sought to determine if short term exposure to high plasma concentration of fatty acid in-vivo was sufficient to alter the cardiac sodium current INa in dog ventricular myocytes. Our results show that delivery of triglycerides and non-esterified fatty acids by infusion of Intralipid™ + heparin (IH) for 8 hour increased the amplitude of INa by 43% and shifted its activation threshold by -5 mV, closer to the resting membrane potential. Steady state inactivation (availability) of the channels was reduced by IH with no changes in recovery from inactivation. As a consequence, INa 'window' current, a strong determinant of intracellular Na(+) and Ca(++) concentrations was significantly increased. The results indicate that increased circulating fatty acids alter INa gating in manners consistent with an increased cardiac excitability and augmentation of intracellular calcium. Moreover, these changes could still be measured after the dogs were left to recover for 12 hours after IH perfusion suggesting lasting changes in INa. Our results indicate that fatty acids rapidly induce cardiac remodeling and suggest that this process may be involved in the development of cardiac dysfunctions associated to insulin resistance and diabetes.
Michael Biet; Nathalie Morin; Ouhida Benrezzak; Foued Naimi; Sylvain Bellanger; Jean-Patrice Bailllargeon; Lucie Chouinard; Nicole Gallo-Payet; Andre C Carpentier; Robert Dumaine
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-15
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Univ. of Sherbrooke.
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