Dietary Omega-3 Fatty Acids and Sudden Cardiac Death

Summary

Principal Investigator: GEORGE BILLMAN
Affiliation: The Ohio State University
Country: USA
Abstract: DESCRIPTION (provided by applicant): Epidemiological studies, clinical trials (patients with myocardial infarction), and animal studies have demonstrated that fish consumption, or diets enriched with fish oil (omega-3 polyunsaturated fatty acids, n-3 PUFAs) supplements, significantly reduced the incidence of sudden cardiac death. However, the mechanisms underlying the relationship between n-3 PUFAs and a reduced risk for cardiac arrhythmias remain to be determined. Therefore, we propose to investigate the safety and efficacy of n-3 PUFAs using a well-established canine model of lethal ventricular arrhythmias. The mechanisms altering cardiac electrophysiology will be examined in cardiac myocytes isolated from the hearts of these animals. The central hypothesis is that chronic treatment with n-3 PUFAs attenuates the electrophysiological abnormalities contributing to sudden cardiac death in a post-myocardial infarction canine model of sudden cardiac death. The following specific aims will be used to test this hypothesis: Specific Aim #1 will test the hypothesis that the chronic ingestion of n-3 PUFA supplements will prevent ischemia-induced tachyarrhythmias (by preventing re-entrant and/or triggered arrhythmias). Specific Aims #2 and #3 will investigate the effects of the chronic administration of n-3 PUFAs on the electrophysiology and calcium regulation of cardiomyocytes prepared from the hearts of the dogs, respectively. In particular, Specific Aim 2 will test the following hypotheses: n-3 PUFAs will a) normalize the sarcolemmal ion currents improving the ventricular myocyte action potential and b) reduce both early and delayed afterdepolarizations in dogs susceptible to ventricular fibrillation. Finally, Specific Aim #3 will test the following hypotheses: a) n-3 PUFAs will block L-type calcium current reducing calcium entry and thereby preventing calcium overload-induced spontaneous calcium release in dogs susceptible to ventricular fibrillation;b) n-3 PUFAs will alter ryanodine receptor function, restoring a more normal sarcoplasmic reticular calcium release in dogs susceptible to ventricular fibrillation;and c) n-3 PUFAs will alter the sarcoplasmic reticular (SR) calcium load, restoring a more normal SR calcium load in the dogs susceptible to ventricular fibrillation. Lay summary: This project will examine the safety of fish oil supplements after a heart attack. This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack.
Funding Period: ----------------2007 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death
    Arun Sridhar
    Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA
    Am J Physiol Regul Integr Comp Physiol 295:R1463-72. 2008
  2. pmc Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness
    Alexey V Glukhov
    Department of Physiology and Cell Biology, College of Veterinary Medicine, Division of Cardiovascular Medicine, and College of Pharmacy, College of Medicine, Dorothy M Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH
    Circ Arrhythm Electrophysiol 6:984-94. 2013
  3. pmc Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death
    Ingrid M Bonilla
    College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA
    J Appl Physiol (1985) 113:1772-83. 2012
  4. pmc Tachy-brady arrhythmias: the critical role of adenosine-induced sinoatrial conduction block in post-tachycardia pauses
    Qing Lou
    Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio 43210 1218, USA
    Heart Rhythm 10:110-8. 2013
  5. pmc Dietary omega-3 fatty acids promote arrhythmogenic remodeling of cellular Ca2+ handling in a postinfarction model of sudden cardiac death
    Andriy E Belevych
    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
    PLoS ONE 8:e78414. 2013
  6. pmc Effect of twitch interval duration on the contractile function of subsequent twitches in isolated rat, rabbit, and dog myocardium under physiological conditions
    Ying Xu
    Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio, USA
    J Appl Physiol (1985) 111:1159-67. 2011
  7. pmc Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect
    George E Billman
    Department of Physiology and Cell Biology, College of Pharmacy, The Ohio State University, Columbus, OH 43210 1218, USA
    Circ Arrhythm Electrophysiol 5:553-60. 2012
  8. pmc Effect of dietary omega-3 fatty acids on the heart rate and the heart rate variability responses to myocardial ischemia or submaximal exercise
    George E Billman
    Dept of Physiology and Cell Biology, Ohio State Univ, 304 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 300:H2288-99. 2011
  9. pmc Effects of dietary omega-3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies
    George E Billman
    Dept of Physiology and Cell Biology, The Ohio State Univ, Columbus, 43210 1218, USA
    Am J Physiol Heart Circ Physiol 298:H1219-28. 2010
  10. pmc Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death
    Andriy E Belevych
    Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, College of Medicine, Columbus, OH 43210, USA
    Cardiovasc Res 84:387-95. 2009

Scientific Experts

  • GEORGE BILLMAN
  • Andriy E Belevych
  • Cynthia A Carnes
  • Ingrid M Bonilla
  • Sandor Gyorke
  • Dmitry Terentyev
  • Radmila Terentyeva
  • Arun Sridhar
  • Alexey V Glukhov
  • Hsiang Ting Ho
  • Yoshinori Nishijima
  • Qing Lou
  • Vadim V Fedorov
  • Pedro Vargas-Pinto
  • Ying Xu
  • Monica Kukielka
  • Brian Hansen
  • Adriana Pedraza-Toscano
  • Lori Hage
  • Brian J Hansen
  • Lori T Hage
  • Raul Weiss
  • Robert L Hamlin
  • Quanhua He
  • Victor P Long
  • Inna Gyorke
  • Bin Liu
  • Paul M L Janssen
  • Nitisha Hiranandani
  • Kaylan M Haizlip
  • Michelle M Monasky
  • Arturo J Cardounel
  • Lance D Wilson
  • Serge Viatchenko-Karpinski
  • Kenneth R Laurita
  • Rebecca Uelmen
  • Gail A Robertson

Detail Information

Publications11

  1. pmc Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death
    Arun Sridhar
    Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA
    Am J Physiol Regul Integr Comp Physiol 295:R1463-72. 2008
    ..These abnormalities may provide a substrate for initiation of postmyocardial infarction ventricular tachyarrhythmias...
  2. pmc Sinoatrial node reentry in a canine chronic left ventricular infarct model: role of intranodal fibrosis and heterogeneity of refractoriness
    Alexey V Glukhov
    Department of Physiology and Cell Biology, College of Veterinary Medicine, Division of Cardiovascular Medicine, and College of Pharmacy, College of Medicine, Dorothy M Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH
    Circ Arrhythm Electrophysiol 6:984-94. 2013
    ..The goal of the present study was to elucidate the mechanism of SAN micro-reentry in canine hearts with post-myocardial infarction (MI) structural remodeling...
  3. pmc Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death
    Ingrid M Bonilla
    College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA
    J Appl Physiol (1985) 113:1772-83. 2012
    ..05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling...
  4. pmc Tachy-brady arrhythmias: the critical role of adenosine-induced sinoatrial conduction block in post-tachycardia pauses
    Qing Lou
    Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio 43210 1218, USA
    Heart Rhythm 10:110-8. 2013
    ..Clinical studies suggest that adenosine may play an important role in SAN dysfunction, but the mechanism remains unclear...
  5. pmc Dietary omega-3 fatty acids promote arrhythmogenic remodeling of cellular Ca2+ handling in a postinfarction model of sudden cardiac death
    Andriy E Belevych
    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
    PLoS ONE 8:e78414. 2013
    ..Furthermore, dietary n-3 PUFAs increase vulnerability of ventricular myocytes to cellular arrhythmia in post-MI VF- hearts by destabilizing intracellular Ca(2+) handling. ..
  6. pmc Effect of twitch interval duration on the contractile function of subsequent twitches in isolated rat, rabbit, and dog myocardium under physiological conditions
    Ying Xu
    Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio, USA
    J Appl Physiol (1985) 111:1159-67. 2011
    ..With the use of randomized cycle lengths, we have distinguished the intrinsic response from the signaling-mediated effects of frequency-dependent activation on myofilament properties and Ca(2+) handling...
  7. pmc Dietary omega-3 fatty acids and susceptibility to ventricular fibrillation: lack of protection and a proarrhythmic effect
    George E Billman
    Department of Physiology and Cell Biology, College of Pharmacy, The Ohio State University, Columbus, OH 43210 1218, USA
    Circ Arrhythm Electrophysiol 5:553-60. 2012
    ..Our aim was to clarify this issue using an established and clinical relevant canine model of sudden cardiac death...
  8. pmc Effect of dietary omega-3 fatty acids on the heart rate and the heart rate variability responses to myocardial ischemia or submaximal exercise
    George E Billman
    Dept of Physiology and Cell Biology, Ohio State Univ, 304 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 300:H2288-99. 2011
    ..These data demonstrate that dietary n-3 PUFA decreased resting (i.e., preexercise or preocclusion) HR and increased resting HRV but did not alter the cardiac response to physiologic challenges...
  9. pmc Effects of dietary omega-3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies
    George E Billman
    Dept of Physiology and Cell Biology, The Ohio State Univ, Columbus, 43210 1218, USA
    Am J Physiol Heart Circ Physiol 298:H1219-28. 2010
    ..Thus dietary n-3 PUFAs did not adversely alter either in vitro or in vivo ventricular contractile function in dogs with healed infarctions...
  10. pmc Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death
    Andriy E Belevych
    Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, College of Medicine, Columbus, OH 43210, USA
    Cardiovasc Res 84:387-95. 2009
    ....
  11. pmc Shortened Ca2+ signaling refractoriness underlies cellular arrhythmogenesis in a postinfarction model of sudden cardiac death
    Andriy E Belevych
    Davis Heart and Lung Research Institute, The Ohio State University Medical Center, 473 W 12th Ave, Columbus, OH 43210, USA
    Circ Res 110:569-77. 2012
    ....