Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 May 10;91(10):4427–4430. doi: 10.1073/pnas.91.10.4427

Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids.

G E Billman 1, H Hallaq 1, A Leaf 1
PMCID: PMC43798  PMID: 8183925

Abstract

A specially prepared dog model of myocardial infarction was used to test the efficacy of the long-chain polyunsaturated fish oil omega 3 fatty acids eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) acids to prevent ischemia-induced malignant cardiac arrhythmias. The dogs had sustained a prior experimental myocardial infarction from ligation of the left anterior descending coronary artery, and a hydraulic cuff was implanted around the left circumflex artery at that operation. After recovery from that procedure the animals were tested during a treadmill exercise test. With compression of the left circumflex artery sensitive animals will predictably develop ventricular fibrillation (VF). In such prepared dogs an emulsion of fish oil fatty acids was infused i.v. over a 50- to 60-min period just before the exercise-plus-ischemia test, and the effect on development of VF was recorded. The infusion was 100 ml of a 10% (vol/vol) emulsion of a fish oil concentrate containing 70% omega 3 fatty acids with free eicosapentaenoic acid and docosahexaenoic acid composing 33.9% and 25.0% of that total, respectively. Alternatively, some animals similarly received an emulsion containing 5 ml of the free fatty acid concentrate plus 5 ml of a triacylglyerol concentrate containing 65% omega 3 fatty acids with eicosapentaenoic acid and docosahexaenoic acid composing 34.0% and 23.6% of that total, respectively. In seven of eight animals the infusion of the fish oil emulsion completely prevented the acute occurrence of VF in the susceptible animals (P < 0.005). In five of five of these animals the subsequent exercise-plus-ischemia test after a similar infusion of an emulsion in which soy bean oil replaced the fish oil fatty acid concentrates resulted in prompt development of VF. Possible mechanisms for this protective effect of omega 3 fatty acids against exercise and ischemia-induced malignant arrhythmias are considered.

Full text

PDF
4428

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bang H. O., Dyerberg J., Hjøorne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand. 1976;200(1-2):69–73. doi: 10.1111/j.0954-6820.1976.tb08198.x. [DOI] [PubMed] [Google Scholar]
  2. Billman G. E. Effect of calcium channel antagonists on cocaine-induced malignant arrhythmias: protection against ventricular fibrillation. J Pharmacol Exp Ther. 1993 Jul;266(1):407–416. [PubMed] [Google Scholar]
  3. Billman G. E. Effect of calcium channel antagonists on susceptibility to sudden cardiac death: protection from ventricular fibrillation. J Pharmacol Exp Ther. 1989 Mar;248(3):1334–1342. [PubMed] [Google Scholar]
  4. Billman G. E., McIlroy B., Johnson J. D. Elevated myocardial calcium and its role in sudden cardiac death. FASEB J. 1991 Aug;5(11):2586–2592. doi: 10.1096/fasebj.5.11.1714409. [DOI] [PubMed] [Google Scholar]
  5. Billman G. E., McIlroy B., Johnson J. D. Elevated myocardial calcium and its role in sudden cardiac death. FASEB J. 1991 Aug;5(11):2586–2592. doi: 10.1096/fasebj.5.11.1714409. [DOI] [PubMed] [Google Scholar]
  6. Billman G. E. Mechanisms responsible for the cardiotoxic effects of cocaine. FASEB J. 1990 May;4(8):2469–2475. doi: 10.1096/fasebj.4.8.2185973. [DOI] [PubMed] [Google Scholar]
  7. Billman G. E. Ro 40-5967, a novel calcium channel antagonist, protects against ventricular fibrillation. Eur J Pharmacol. 1992 Dec 15;229(2-3):179–187. doi: 10.1016/0014-2999(92)90553-g. [DOI] [PubMed] [Google Scholar]
  8. Billman G. E. The calcium channel antagonist, flunarizine, protects against ventricular fibrillation. Eur J Pharmacol. 1992 Mar 3;212(2-3):231–235. doi: 10.1016/0014-2999(92)90334-z. [DOI] [PubMed] [Google Scholar]
  9. Burr M. L., Fehily A. M., Gilbert J. F., Rogers S., Holliday R. M., Sweetnam P. M., Elwood P. C., Deadman N. M. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989 Sep 30;2(8666):757–761. doi: 10.1016/s0140-6736(89)90828-3. [DOI] [PubMed] [Google Scholar]
  10. Dolecek T. A. Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med. 1992 Jun;200(2):177–182. doi: 10.3181/00379727-200-43413. [DOI] [PubMed] [Google Scholar]
  11. Ferrier G. R. Digitalis arrhythmias: role of oscillatory afterpotentials. Prog Cardiovasc Dis. 1977 May-Jun;19(6):459–474. doi: 10.1016/0033-0620(77)90010-x. [DOI] [PubMed] [Google Scholar]
  12. Hallaq H., Sellmayer A., Smith T. W., Leaf A. Protective effect of eicosapentaenoic acid on ouabain toxicity in neonatal rat cardiac myocytes. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7834–7838. doi: 10.1073/pnas.87.20.7834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hallaq H., Smith T. W., Leaf A. Modulation of dihydropyridine-sensitive calcium channels in heart cells by fish oil fatty acids. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1760–1764. doi: 10.1073/pnas.89.5.1760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Honoré E., Barhanin J., Attali B., Lesage F., Lazdunski M. External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1937–1941. doi: 10.1073/pnas.91.5.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lappi M. D., Billman G. E. Effect of ryanodine on ventricular fibrillation induced by myocardial ischaemia. Cardiovasc Res. 1993 Dec;27(12):2152–2159. doi: 10.1093/cvr/27.12.2152. [DOI] [PubMed] [Google Scholar]
  16. Leaf A. Health claims: omega-3 fatty acids and cardiovascular disease. Nutr Rev. 1992 May;50(5):150–154. doi: 10.1111/j.1753-4887.1992.tb01310.x. [DOI] [PubMed] [Google Scholar]
  17. Lee J. A., Allen D. G. Mechanisms of acute ischemic contractile failure of the heart. Role of intracellular calcium. J Clin Invest. 1991 Aug;88(2):361–367. doi: 10.1172/JCI115311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McLennan P. L., Abeywardena M. Y., Charnock J. S. Dietary fish oil prevents ventricular fibrillation following coronary artery occlusion and reperfusion. Am Heart J. 1988 Sep;116(3):709–717. doi: 10.1016/0002-8703(88)90328-6. [DOI] [PubMed] [Google Scholar]
  19. McLennan P. L., Bridle T. M., Abeywardena M. Y., Charnock J. S. Comparative efficacy of n-3 and n-6 polyunsaturated fatty acids in modulating ventricular fibrillation threshold in marmoset monkeys. Am J Clin Nutr. 1993 Nov;58(5):666–669. doi: 10.1093/ajcn/58.5.666. [DOI] [PubMed] [Google Scholar]
  20. Merillat J. C., Lakatta E. G., Hano O., Guarnieri T. Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation. Circ Res. 1990 Nov;67(5):1115–1123. doi: 10.1161/01.res.67.5.1115. [DOI] [PubMed] [Google Scholar]
  21. du Toit E. F., Opie L. H. Modulation of severity of reperfusion stunning in the isolated rat heart by agents altering calcium flux at onset of reperfusion. Circ Res. 1992 May;70(5):960–967. doi: 10.1161/01.res.70.5.960. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES