title: Dietary omega-3 fatty acids promote arrhythmogenic remodeling of cellular Ca2+ handling in a postinfarction model of sudden cardiac death.
abstract: It has been proposed that dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) can reduce the risk of ventricular arrhythmias in post-MI patients. Abnormal Ca(2+) handling has been implicated in the genesis of post-MI ventricular arrhythmias. Therefore, we tested the hypothesis that dietary n-3 PUFAs alter the vulnerability of ventricular myocytes to cellular arrhythmia by stabilizing intracellular Ca(2+) cycling. To test this hypothesis, we used a canine model of post-MI ventricular fibrillation (VF) and assigned the animals to either placebo (1 g/day corn oil) or n-3 PUFAs (1-4 g/day) groups. Using Ca(2+) imaging techniques, we examined the intracellular Ca(2+) handling in myocytes isolated from post-MI hearts resistant (VF-) and susceptible (VF+) to VF. Frequency of occurrence of diastolic Ca(2+) waves (DCWs) in VF+ myocytes from placebo group was significantly higher than in placebo-treated VF- myocytes. n-3 PUFA treatment did not decrease frequency of DCWs in VF+ myocytes. In contrast, VF- myocytes from the n-3 PUFA group had a significantly higher frequency of DCWs than myocytes from the placebo group. In addition, n-3 PUFA treatment increased beat-to-beat alterations in the amplitude of Ca(2+) transients (Ca(2+) alternans) in VF- myocytes. These n-3 PUFAs effects in VF- myocytes were associated with an increased Ca(2+) spark frequency and reduced sarcoplasmic reticulum Ca(2+) content, indicative of increased activity of ryanodine receptors. Thus, dietary n-3 PUFAs do not alleviate intracellular Ca(2+) cycling remodeling in myocytes isolated from post-MI VF+ hearts. Furthermore, dietary n-3 PUFAs increase vulnerability of ventricular myocytes to cellular arrhythmia in post-MI VF- hearts by destabilizing intracellular Ca(2+) handling.
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, the Ohio State University, Columbus, Ohio, United States of America ; Department of Physiology and Cell Biology, College of Medicine, the Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Andriy E
authors.initials: AE
authors.lastname: Belevych
authors.forename: Hsiang-Ting
authors.initials: HT
authors.lastname: Ho
authors.forename: Radmila
authors.initials: R
authors.lastname: Terentyeva
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Bonilla
authors.forename: Dmitry
authors.initials: D
authors.lastname: Terentyev
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
authors.forename: Sandor
authors.initials: S
authors.lastname: Gyorke
authors.forename: George E
authors.initials: GE
authors.lastname: Billman
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism*; D016757:Death, Sudden, Cardiac / Q000473:pathology*; D004032:Diet / Q000379:methods; D004285:Dogs; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015525:Fatty Acids, Omega-3; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium