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Raised plasma non-esterified fatty acids (NEFA) during ischaemia: implications for arrhythmias

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Lipid metabolism in the normoxic and ischaemic heart
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Summary

Raised plasma non-esterified fatty acids (NEFA) have been directly implicated in the development of serious ventricular arrhythmias and death during acute myocardial infarction.

Since this was first proposed by Oliver and Kurien in 1970, clinical and experimental evidence has been conflicting, but results of clinical studies with antilipolytic drugs suggested a reduction in ventricular tachycardia. Lowering of raised NEFA by antilipolytic therapy in dogs was effective, whilst raising NEFA, either by intravascular lipolysis or direct infusion, failed to precipitate VF.

An alternative hypothesis is proposed, which suggests that a fatty acid — triglyceride energy wasting cycle operates at different rates within the ischaemic heart, and causes differential rates of K+ loss, leading to ventricular fibrillation.

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References

  1. Borbola Jr J Papp Gy J, Szekeres L (1976) Effect of free fatty acids on the automaticity of the sinus node and Purkinje fibres. In: Szekeres L, Papp Gy J (eds) Symposium on pharmacology of the heart. Akademiai Kiado, Budapest, pp 75–80

    Google Scholar 

  2. Borbola Jr J, Süsskand K, Siess M, Szekeres L (1977) The effect of arachidonic acid in isolated atria of guinea pigs. Eur J Pharmacol 41: 27–36

    Article  PubMed  CAS  Google Scholar 

  3. Brownsey RW, Brundt RV (1977) The effect of adrenaline-induced endogenous lipolysis upon the mechanical and metabolic performance of ischaemically perfused rat hearts. Clin Sci Mol Med 53: 513–521

    PubMed  CAS  Google Scholar 

  4. Carlström S, Christensson B (1971) Plasma glycerol concentration in patients with myocardial ischaemia and arrhythmias. Br Heart J 33: 884–888

    Article  PubMed  Google Scholar 

  5. Ceremuzynski L, Herbaczynska-Cedro K, Ruthven CRJ, Goodwin BL, Weg MH, Lax PM, Sandler M (1983) Augmented excretion of catecholamine metabolites in myocardial infarction of mild course and increased excretion of free catecholamines in the complicated diseases. In: Refsum H, Jynge P, Mjes OD (eds) Myocardial ischaemiaandprotection. Churchill Livingstone, Edingburgh, pp 101–108

    Google Scholar 

  6. Ceremuzynski L, Staszewska-Barczak J, Herbazynska-Cedro K (1969) Cardiac rhythm disturbances and the release of catecholamines after acute coronary occlusion in dogs. Cardiovasc Res 3: 190–197

    Article  PubMed  CAS  Google Scholar 

  7. Cowan JW, Vaughan Williams EM (1977) The effects of palmitate on intracellular potentials recorded from Langendorff-perfused guinea-pig hearts in normoxia and hypoxia, and during perfusion at reduced rate of flow. J Mol Cell Cardiol 9: 327–342

    Article  PubMed  CAS  Google Scholar 

  8. De Leiris J, Opie LH, Lubbe WH (1975) Effects of free fatty acid and glucose on enzyme release in experimental myocardial infarction. Nature 253: 746–747

    Article  PubMed  Google Scholar 

  9. Ebert PA, Van der Beek RB, Allgood RJ, Sabiston DC (1970) Effect of chronic cardiac denervation on arrhythmias after coronary ligation. Cardiovasc Res 4: 141–147

    Article  PubMed  CAS  Google Scholar 

  10. Gaudeul Y, Karagueuzian HS, De Leiris J (1979) Deleterious effects of endogenous catecholamines on hypoxic myocardial cells following reoxygenation. J Moll Cell Cardiol 11: 717–731

    Article  Google Scholar 

  11. Goodman DS (1958) The interaction of human serum albumin with long-chain fatty acids anions. Am J Chem Soc 80: 3892–3898

    Article  CAS  Google Scholar 

  12. Greenough III WB, Crespin SR, Steinberg D (1969) Infusion of long-chain fatty acid anions by continuous-flow centrifugation. J Clin Inv 48: 1923–1933

    Article  CAS  Google Scholar 

  13. Gupta DK, Young R, Jewett DE, Hartog M, Opie LH (1969) Increased plasma free-fatty-acid concentrations and their significance in patients with acute myocardial infarction. Lancet 2: 1209–1213

    Article  PubMed  CAS  Google Scholar 

  14. Hagenfeldt L, Wester PO (1973) Plasma levels of individual free fatty acids in patients with acute myocardial infarction. Acta Med Scand 194: 357–362

    Article  PubMed  CAS  Google Scholar 

  15. Harada H, Azuma J, Hasegawa H, Ohta H, Yamauchi K, Ogura K, Awata N, Sawamura A, Sperelakis N, Kishimoto S (1984) Enhanced suppression of myocardial slow action potentials during hypoxia by free fatty acids. J Mol Cell Cardiol 16: 261–276

    Article  PubMed  CAS  Google Scholar 

  16. Henderson AH, Most AS, Parmley WW, Gorlin R, Sonnenblick EH (1970) Depression of myocardial contractility in rats by free fatty acids during hypoxia. Circ Res 26: 439–449

    Article  PubMed  CAS  Google Scholar 

  17. Hough FS, Gevers W (1975) Catecholamine release as mediator of intracellular enzyme activation in ischaemic perfused rat hearts. S Afr Med J 49: 538–543

    PubMed  CAS  Google Scholar 

  18. Hunneman DH, Schweickhardt C (1982) Mass fragmentographic determination of myocardial free fatty acids. J Mol Cell Cardiol 14: 339–351

    Article  PubMed  CAS  Google Scholar 

  19. Idell-Wenger JA, Neely JR (1977) Effects of ischemia on myocardial fatty acid oxidation. In: Lefer AM, Rovetto J (eds) Pathophysiology and therapeutics of myocardial ischemia. Spectrum Publications, New York, pp 227–238

    Google Scholar 

  20. Jesmok GJ, Warltier DC, Gross GJ, Hardman HF (1978) Transmural triglycerides in acute myocardial ischaemia. Cardiovasc Res 12: 659–665

    Article  PubMed  CAS  Google Scholar 

  21. Kaplinsky E, Ogawa S, Balke W, Dreifus LS (1979) Two periods of early ventricular arrhythmias in the canine acute myocardial infarction model. Circulation 60: 397–403

    Article  PubMed  CAS  Google Scholar 

  22. Kim RS, Bihler I, Labella FS (1985) Calcium — translocating and cardiotonic properties of oxidation-products of linoleic-acid. Can J Physiol Pharmacol 63: 1392–1397

    Article  PubMed  CAS  Google Scholar 

  23. Kostis JB, Mavrogeorgis EA, Horstmann E, Gotzoyannis S (1973) Effect of high concentrations of free fatty acids on the ventricular fibrillation threshold in normal dogs and dogs with acute myocardial infarction. Cardiology 58: 89–98

    Article  PubMed  CAS  Google Scholar 

  24. Kurien VA, Oliver MF (1970) A metabolic cause of arrhythmias during acute myocardial hypoxia. Lancet 1: 813–815

    Article  PubMed  CAS  Google Scholar 

  25. Kurien VA, Yates PA, Oliver MF (1969) Free fatty acids, heparin, and arrhythmias during experimental myocardial infarction. Lancet 2: 185–187

    Article  PubMed  CAS  Google Scholar 

  26. Kurien VA, Yates PA, Oliver MF (1971) The role of free fatty acids in the production of ventricular arrhythmias after acute coronary artery occlusion. Eur J Clin Inv 1: 225–241

    CAS  Google Scholar 

  27. Liedtke AJ (1981) Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Progr Cardiov Dis 23: 321–336

    Article  PubMed  CAS  Google Scholar 

  28. Liedtke Ai, Nellis S, Neely JR (1978) Effects of excess free fatty acids on mechanical and metabolic function in normal and ischemic myocardium in swine. Circ Res 43: 652–661

    Article  PubMed  CAS  Google Scholar 

  29. Luxton MR, Miller NE, Oliver MF (1976) Antilipolytic therapy in angina pectoris. Reduction of exercise-induced ST-segment depression. Br Heart J 38: 1204–1208

    Article  PubMed  CAS  Google Scholar 

  30. Martin C, MeesmannW (1985) Antiarrhythmic effect of regional myocardial chemical sympathectomy in the early phase of coronary artery occlusion in dogs. J Cardiovasc Pharmacol 7 (Suppl 5): 76–80

    Article  Google Scholar 

  31. Miller NE, Mjes OD, Oliver MF (1976) Relationship of epicardial ST-segment elevation to the plasma free fatty acid/albumin ratio during coronary occlusion in dogs. Clin Sci Mol Med 51: 209–213

    PubMed  CAS  Google Scholar 

  32. Murnaughan MF (1981) Effect of fatty acids on the ventricular arrhythmia threshold in the isolated heart of the rabbit. Br J Pharmac 73: 909–915

    Article  Google Scholar 

  33. Nelson PG (1970) Effect of heparin on serum free-fatty-acids, plasma catecholamines, and the incidence of arrhytmias following acute myocardial infarction. Br Med J 3: 735–737

    Article  PubMed  CAS  Google Scholar 

  34. Oliver MF, Kurien VA, Greenwood TW (1968) Relation between serum free-fatty-acids and arrhythmias and death after acute myocardial infarction. Lancet 1: 710–714

    Article  PubMed  CAS  Google Scholar 

  35. Oliver MF, Yates PA (1971/2) Induction of ventricular arrhythmias by elevation of arterial free fatty acids in experimental myocardial infarction. Cardiology 56: 359–364

    Article  CAS  Google Scholar 

  36. Opie LH, Lubbe WF (1975) Are free fatty acids arrhythmogenic? J Moll Cell Cardiol 7: 155–159

    Article  CAS  Google Scholar 

  37. Opie LH, Norris RN, Thomas M, Holland AJ, Owen P, Van Noorden S (1971) Failure of high concentrations of circulating free fatty acids to provoke arrhythmias in experimental myocardial infarction. Lancet 1: 818–822

    Article  PubMed  CAS  Google Scholar 

  38. Opie LH, Owen P, Riemersma RA (1973) Relative rates of oxidation of glucose and free fatty acids in ischaemic and non-ischaemic myocardium after coronary artery ligation in the dog. Eur J Clin Inv 3: 419–435

    Article  CAS  Google Scholar 

  39. Ravens KG, Jipp P (1972) Die freien Plasmafettsäuren in der Frühphase eines Myocardinfarkts. Arzneim Forsch 22: 1831–1835

    CAS  Google Scholar 

  40. Reimann R, Schwandt P (1971) Frischer Herzinfarkt and freie Fettsäuren. Dtsch Med W Schr 96: 93–96

    Article  CAS  Google Scholar 

  41. Riemersma RA (1981) Factors regulating normal and ischaemic myocardial substrate metabolism. Adv Physiol Sci 8: 109–119

    CAS  Google Scholar 

  42. Riemersma RA, Logan RL, Russell DC, Smith HJ, Simpson J, Oliver MF (1982) Effect of heparin on plasma free fatty acid concentrations after acute myocardial infarction. Br Heart J 48: 134–139

    Article  PubMed  CAS  Google Scholar 

  43. Rowe MJ, Neilson JMM, Oliver MF (1975) Control of ventricular arrhythmias during myocardial infarction by antilipolytic treatment using a nicotinic-acid analogue. Lancet 1: 295–308

    Article  PubMed  CAS  Google Scholar 

  44. Scheuer J, Brachfeld N (1966) Myocardial uptake and fractional distribution of palmitate -1 -C14 by the ischemic dog heart. Metabolism 15: 945–954

    Article  PubMed  CAS  Google Scholar 

  45. Shug AL, Thomsen JH, Folts JD, Bittar N, Klein MI, Koke JR, Hutch PJ (1978) Changes in tissue levels of carnitine and other metabolites during myocardial ischemia and anoxia. Arch Biochem Biophys 187: 25–33

    Article  PubMed  CAS  Google Scholar 

  46. Simonsen S, Kjekshus JK (1978) The effect of free fatty acids on myocardial oxygen consumption during atrial pacing and catecholamine infusion in man. Circulation 58: 484–491

    Article  PubMed  CAS  Google Scholar 

  47. Smith ER, Duce BR (1974) Anti-arryhthmic and serum free fatty acid lowering effects of 5-fluoronicotinyl alcohol following experimentally induced myocardial infarction in the dog. Cardiovasc Res 8: 550–561

    Article  PubMed  CAS  Google Scholar 

  48. Takano S (1976) Genetic studies on the arryhthmia in acute myocardial infarction with special reference to serum free fatty acid level. Jpn Cire J 40: 287–297

    Article  CAS  Google Scholar 

  49. Tansey MJB, Opie LH (1983) Relation between plasma free fatty acids and arrhythmias within the first twelve hours of acute myocardial infarction. Lancet 2: 419–422

    Article  PubMed  CAS  Google Scholar 

  50. Thomas JX Jr, Randah WC, Jones CE (1981) Protective effect of chronic versus acute cardiac denervation on contractile force during coronary occlusion. Am Heart J 102: 157–161

    Article  PubMed  Google Scholar 

  51. Van der Vusse GJ, Prinzen FW, Coumans WA, Kruger R, Verlaan C, Reneman RS (1980) Assessment of myocardial ischemia using hemodynamic and biochemical variables with special reference to elevated arterial free fatty acid concentration by heparin. Adv Clin Cardiol 1: 407–421

    Google Scholar 

  52. Van der Vusse GJ, Roemen Th HM, Prinzen FW, Coumans WA, Reneman RS (1982) Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischemic conditions. Circ Res 50: 538–546

    Article  PubMed  Google Scholar 

  53. Verrier RL, Thomson PL, Lown B (1974) Ventricular vulnerability during sympathetic stimulation; role of heart rate and blood pressure. Cardiovasc Res 8: 602–610

    Article  PubMed  CAS  Google Scholar 

  54. Vetter NJ, Strange RC, Adams W, Oliver MF (1974) Initial metabolic and hormonal response to acute myocardial infarction. Lancet 1: 284–288

    Article  PubMed  CAS  Google Scholar 

  55. Vik-Mo H, Mjøs OD (1981) Influence of free fatty acids ( FFA) on myocardial oxygen demand and ischemic injury. Am J Cardiol 48: 361–365

    Article  PubMed  CAS  Google Scholar 

  56. Vik-Mo H, Riemersma RA, Mjøs OD, Oliver MF (1979) Effect of myocardial ischaemia and antilipolytic agents on lipolysis and fatty acid metabolism in the in situ dog heart. Scand J Clin Lab Inv 39: 559–568

    Article  CAS  Google Scholar 

  57. Webb SW, Adgey AM, Pantridge JF (1972) Autonomic disturbance at onset of acute myocardial infarction. Br Med J 3: 89–92

    Article  PubMed  CAS  Google Scholar 

  58. Willebrands AF (1979) Personal communication

    Google Scholar 

  59. Wolf R, Beck OA, Hochrein H (1974) Der Einluß von Heparin auf die Häufigkeit von Rhythmusstörungen beim akuten Myokardinfarkt. Dtsch Med Wschr 99: 1549–1553.

    Article  PubMed  CAS  Google Scholar 

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H. Stam G. J. van der Vusse

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© 1987 Springer-Verlag Berlin Heidelberg

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Riemersma, R.A. (1987). Raised plasma non-esterified fatty acids (NEFA) during ischaemia: implications for arrhythmias. In: Stam, H., van der Vusse, G.J. (eds) Lipid metabolism in the normoxic and ischaemic heart. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-08390-1_22

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  • DOI: https://doi.org/10.1007/978-3-662-08390-1_22

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-662-08392-5

  • Online ISBN: 978-3-662-08390-1

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