Document Detail


Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival.
MedLine Citation:
PMID:  23103493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondrial dysfunction in heart failure includes greater susceptibility to mitochondrial permeability transition (MPT), which may worsen cardiac function and decrease survival. Treatment with a mixture of the n3 polyunsaturated fatty acids (n3 PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is beneficial in heart failure patients and increases resistance to MPT in animal models. We assessed whether DHA and EPA have similar effects when given individually, and whether they prolong survival in heart failure. Male δ-sarcoglycan null cardiomyopathic hamsters were untreated or given either DHA, EPA, or a 1:1 mixture of DHA + EPA at 2.1% of energy intake. Treatment did not prolong survival: mean survival was 298 ± 15 days in untreated hamsters and 335 ± 17, 328 ± 14, and 311 ± 15 days with DHA, EPA, and DHA + EPA, respectively (n = 27-32/group). A subgroup of cardiomyopathic hamsters treated for 26 wk had impaired left ventricular function and increased cardiomyocyte apoptosis compared with normal hamsters, which was unaffected by n3 PUFA treatment. Evaluation of oxidative phosphorylation in isolated subsarcolemmal and interfibrillar mitochondria with substrates for complex I or II showed no effect of n3 PUFA treatment. On the other hand, interfibrillar mitochondria from cardiomyopathic hamsters were significantly more sensitive to Ca(2+)-induced MPT, which was completely normalized by treatment with DHA and partially corrected by EPA. In conclusion, treatment with DHA or EPA normalizes Ca(2+)-induced MPT in cardiomyopathic hamsters but does not prolong survival or improve cardiac function. This suggest that greater susceptibility to MPT is not a contributor to cardiac pathology and poor survival in heart failure.
Authors:
Tatiana F Galvao; Ramzi J Khairallah; Erinne R Dabkowski; Bethany H Brown; Peter A Hecker; Kelly A O'Connell; Karen M O'Shea; Hani N Sabbah; Sharad Rastogi; Caroline Daneault; Christine Des Rosiers; William C Stanley
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-26
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  304     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-02-20     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H12-21     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Apoptosis / drug effects
Calcium / metabolism
Cardiomyopathy, Dilated / drug therapy*,  genetics,  metabolism,  pathology,  physiopathology
Cardiotonic Agents / pharmacology*
Cricetinae
Disease Models, Animal
Docosahexaenoic Acids / pharmacology*
Drug Therapy, Combination
Eicosapentaenoic Acid / pharmacology*
Heart Failure / drug therapy*,  genetics,  metabolism,  pathology,  physiopathology
Male
Mitochondria, Heart / drug effects*,  metabolism,  pathology
Mitochondrial Membrane Transport Proteins / drug effects*,  metabolism
Myocytes, Cardiac / drug effects*,  metabolism,  pathology
Oxidative Phosphorylation / drug effects
Phospholipids / metabolism
Sarcoglycans / deficiency,  genetics
Stroke Volume / drug effects
Time Factors
Ventricular Function, Left / drug effects
Grant Support
ID/Acronym/Agency:
HL-072751/HL/NHLBI NIH HHS; HL-074237/HL/NHLBI NIH HHS; HL-101434/HL/NHLBI NIH HHS; P30 DK079637/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Mitochondrial Membrane Transport Proteins; 0/Phospholipids; 0/Sarcoglycans; 0/mitochondrial permeability transition pore; 25167-62-8/Docosahexaenoic Acids; AAN7QOV9EA/Eicosapentaenoic Acid; SY7Q814VUP/Calcium
Comments/Corrections

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