Prevention of Sudden Cardiac Death by Dietary Pure ω-3 Polyunsaturated Fatty Acids in Dogs

Background —Rat diets high in fish oil have been shown to be protective against ischemia-induced fatal ventricular arrhythmias. Increasing evidence suggests that this may also apply to humans. To confirm the evidence in animals, we tested a concentrate of the free fish-oil fatty acids and found them to be antiarrhythmic. In this study, we tested the pure free fatty acids of the 2 major dietary ω-3 polyunsaturated fatty acids in fish oil: cis-5,8,11,14,17-eicosapentaenoic acid (C20:5ω-3) and cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6ω-3), and the parent ω-3 fatty acid in some vegetable oils, cis-9,12,15-α-linolenic acid (C18:3ω-3), administered intravenously on albumin or a phospholipid emulsion. Methods and Results —The tests were performed in a dog model of cardiac sudden death. Dogs were prepared with a large anterior wall myocardial infarction produced surgically and an inflatable cuff placed around the left circumflex coronary artery. With the dogs running on a treadmill 1 month after the surgery, occlusion of the left circumflex artery regularly produced ventricular fibrillation in the control tests done 1 week before and after the test, with the ω-3 fatty acids administered intravenously as their pure free fatty acid. With infusion of the eicosapentaenoic acid, 5 of 7 dogs were protected from fatal ventricular arrhythmias ( P <0.02). With docosahexaenoic acid, 6 of 8 dogs were protected, and with α-linolenic acid, 6 of 8 dogs were also protected ( P <0.004 for each). The before and after control studies performed on the same animal all resulted in fatal ventricular arrhythmias, from which they were defibrillated. Conclusions —These results indicate that purified ω-3 fatty acids can prevent ischemia-induced ventricular fibrillation in this dog model of sudden cardiac death.

[1]  N. Sheard Fish consumption and risk of sudden cardiac death. , 2009, Nutrition reviews.

[2]  A. Leaf,et al.  Fatty acids suppress voltage-gated Na+ currents in HEK293t cells transfected with the alpha-subunit of the human cardiac Na+ channel. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  G. Billman,et al.  Dietary n-3 fatty acids in the prevention of cardiac arrhythmias. , 1998, Current opinion in clinical nutrition and metabolic care.

[4]  A. Leaf,et al.  Fatty acids suppress voltage-gated Na 1 currents in HEK 293 t cells transfected with the a-subunit of the human cardiac Na 1 channel ( transfection y eicosapentaenoic acid ) , 1998 .

[5]  G. Billman,et al.  Prevention of ischemia-induced cardiac Sudden death by n−3 polyunsaturated fatty acids in dogs , 1997, Lipids.

[6]  E. Toft,et al.  [n-3 polyunsaturated fatty acids, heart rate variability and ventricular arrhythmias in post-AMI-patients. A clinical controlled trial]. , 1997, Ugeskrift for laeger.

[7]  A. Leaf,et al.  Differential effects of various eicosanoids on the production or prevention of arrhythmias in cultured neonatal rat cardiac myocytes. , 1997, Prostaglandins.

[8]  W. Lederer,et al.  Suppression of voltage-gated L-type Ca2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Cunnane,et al.  The majority of dietary linoleate in growing rats is beta-oxidized or stored in visceral fat. , 1997, The Journal of nutrition.

[10]  A. Dart,et al.  Dietary fish oil prevents reperfusion Ins(1,4,5)P3 release in rat heart: possible antiarrhythmic mechanism. , 1996, The American journal of physiology.

[11]  G. Billman,et al.  The effects of mibefradil, a novel calcium channel antagonist on ventricular arrhythmias induced by myocardial ischemia and programmed electrical stimulation. , 1996, The Journal of pharmacology and experimental therapeutics.

[12]  A. Leaf,et al.  Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[13]  A. Leaf,et al.  Protective effects of free polyunsaturated fatty acids on arrhythmias induced by lysophosphatidylcholine or palmitoylcarnitine in neonatal rat cardiac myocytes. , 1996, European journal of pharmacology.

[14]  A. Leaf,et al.  Blocking effects of polyunsaturated fatty acids on Na+ channels of neonatal rat ventricular myocytes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  T. Raghunathan,et al.  Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. , 1995, JAMA.

[16]  A. Leaf,et al.  Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. Leaf,et al.  Prevention and termination of beta-adrenergic agonist-induced arrhythmias by free polyunsaturated fatty acids in neonatal rat cardiac myocytes. , 1995, Biochemical and biophysical research communications.

[18]  S. Otsuji,et al.  Antiarrhythmic effects of eicosapentaenoic acid during myocardial infarction--enhanced cardiac microsomal (Ca(2+)-Mg2+)-ATPase activity. , 1994, Japanese circulation journal.

[19]  A. Jacobs,et al.  Do fish oils prevent restenosis after coronary angioplasty? , 1994, Circulation.

[20]  A. Leaf,et al.  Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[21]  P. Touboul,et al.  Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease , 1994, The Lancet.

[22]  G. Billman,et al.  Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Mehta,et al.  Dietary fish oil supplementation attenuates myocardial dysfunction and injury caused by global ischemia and reperfusion in isolated rat hearts. , 1993, The Journal of nutrition.

[24]  W. Koroshetz,et al.  Phospholipase A2 (PLA2) activity in gerbil brain: characterization of cytosolic and membrane-associated forms and effects of ischemia and reperfusion on enzymatic activity. , 1993, Journal of lipid mediators.

[25]  P. McLennan Relative effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on cardiac arrhythmias in rats. , 1993, The American journal of clinical nutrition.

[26]  J. Hamilton Binding of Fatty Acids to Albumin: A Case Study of Lipid-Protein Interactions , 1992 .

[27]  M. Abeywardena,et al.  Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey. , 1992, American heart journal.

[28]  C. E. Hock,et al.  Influence of dietary n-3 fatty acids on myocardial ischemia and reperfusion. , 1990, The American journal of physiology.

[29]  J. Bonventre,et al.  Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[30]  P. Elwood,et al.  EFFECTS OF CHANGES IN FAT, FISH, AND FIBRE INTAKES ON DEATH AND MYOCARDIAL REINFARCTION: DIET AND REINFARCTION TRIAL (DART) , 1989, The Lancet.

[31]  D. Cistola,et al.  Ionization and phase behavior of fatty acids in water: application of the Gibbs phase rule. , 1988, Biochemistry.

[32]  D. Cistola,et al.  Carbon 13 NMR studies of saturated fatty acids bound to bovine serum albumin. I. The filling of individual fatty acid binding sites. , 1987, The Journal of biological chemistry.

[33]  P. Weber,et al.  A new era for science in nutrition. , 1987, The American journal of clinical nutrition.

[34]  M. Abeywardena,et al.  Influence of dietary lipids on arrhythmias and infarction after coronary artery ligation in rats. , 1985, Canadian journal of physiology and pharmacology.

[35]  H. L. Stone,et al.  Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death. , 1984, Circulation.

[36]  H. L. Stone,et al.  Baroreceptor Reflex Control of Heart Rate: A Predictor of Sudden Cardiac Death , 1982, Circulation.

[37]  H. Bazett,et al.  AN ANALYSIS OF THE TIME‐RELATIONS OF ELECTROCARDIOGRAMS. , 1997 .