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Metabolic Therapy for Heart Disease: Impact of Trimetazidine

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References

  1. Crea F, Gaspardone A. New look to an old symptom: angina pectoris. Circulation 1997;96:3766–3773.

    CAS  PubMed  Google Scholar 

  2. Li RA, Leppo M, Miki T, Seino S, Marbán E. Molecular Basis of Electrocardiographic ST-Segment Elevation. Circ Res 2001;87:837–839.

    Google Scholar 

  3. Packer M. Combined beta-adrenergic and calcium-entry blockade in angina patients. N Engl J Med 1989;320,709–718.

    CAS  PubMed  Google Scholar 

  4. Akhras F, Jackson G. Efficacy of nifedipine and isosorbide mononitrate in combination with atenolol in stable angina. Lancet 1991;338:1036–1039.

    Article  CAS  PubMed  Google Scholar 

  5. Savonitto S, Ardissino D, Egstrup K, Rasmussen K, Bae AE, Omland T, et al. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. J Am Coll Cardiol 1996;27:311–316.

    CAS  PubMed  Google Scholar 

  6. Fox KM, Mulcahy D, Findlay I, Ford I, Dargie HJ, on behalf of the TIBET Study Group. The total Ischemic Burden European Trial (TIBET). Eur Heart J 1996;17:96–103.

    CAS  PubMed  Google Scholar 

  7. Thandani U. Management of patients with chronic stable angina low risk for serious cardiac events. Am J Cardiol 1997;79:24–30.

    Google Scholar 

  8. Lopaschuk GD, Belke DD, Gamble J, Itoi T, Schonekess BO. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochem Biophys Acta 1994;1213:263–276.

    CAS  PubMed  Google Scholar 

  9. Wisneski JA, Gertz EW, Neese RA, Mayr M. Myocardial metabolism of free fatty acids. Studies with 14C-labeled substrates in humans. J Clin Invest 1987;79:359–366.

    CAS  PubMed  Google Scholar 

  10. Wisneski JA, Gertz EW, Neese RA, Gruenke LD, Morris DL, Craig JC. Metabolic fate of extracted glucose in normal human myocardium. J Clin Invest 1985;76:1819–1827.

    CAS  PubMed  Google Scholar 

  11. Gertz EW, Wisneski JA, Stanley WC, Neese RA. Myocardial substrate utilization during exercise in humans. Dual carbon-labeled carbohydrate isotope experiments.

  12. Lopaschuk GD, Stanley WC. Glucose metabolism in the ischemic heart. Circulation 1997;95:313–315.

    CAS  PubMed  Google Scholar 

  13. Budingen T. Uber die Moglichkeit einer Ernahrungsbehandlund des Herzmuskels durch Einbringer von Traubenzuckerlosungen in den groben Kreislauf. Dt. Arch. Klin. Med. 1914;114:534–579.

    Google Scholar 

  14. Sodi-Pollares D, Testelli MR, Fishleder BL, Bisteni A, Medrano GA, DeMicheli A. Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction. Am J Cardiol 1962;9:166–181.

    Google Scholar 

  15. Fath-Ordoubadi F, Beatt KJ. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction. An overview of randomized placebo-controlled trials. Circulation 1997;96:1132–1136.

    Google Scholar 

  16. Diaz R, Paolasso EA, Piegas LS, et al. Metabolic modulation of acute myocardial infarction: the ECLA Glucose-Insulin-Potassium Pilot Trial. Circulation 1998;98:2227–2234.

    CAS  PubMed  Google Scholar 

  17. Ceremuzynski L, Budaj A, Czepiel A, et al. Low-dose glucose-insulin-potassium is ineffective in acute myocardial infarction: results of a randomized multicenter pol-GIK trial. Cardiovas Drugs Ther 1999;13:191–200.

    CAS  Google Scholar 

  18. Stanley WC, Lopaschuk GD, Hall JL, McCormack JG. Regulation of myocardial carbohydrate metabolism under normal and ischemic conditions. Potential for pharmacological interventions. Cardiovas Res 1997;33:243–257.

    CAS  Google Scholar 

  19. Lopaschuk GD, Belke DD, Gamble J, Itoi T, Schonekess BO. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochem Biophys Acta 1994;1213:263–276.

    CAS  PubMed  Google Scholar 

  20. Lassers BW, Wahqvist ML, Kaijser L, Carlson LA. Effect of nicotinic acid on myocardial metabolism in man at rest and during exercise. J Appl Physiol 1972;33:72–80.

    CAS  PubMed  Google Scholar 

  21. Rowe MJ, Dolder MA, Kirby BJ, Oliver MF. Effect of a nicotinic-acid analogue on raised plasma-free-fatty-acids after acute myocardial infarction. Lancet 1973;ii:814–818.

    Google Scholar 

  22. Rowe MJ, Neilson JMM, Oliver MF. Control of ventricular arrhythmias during myocardial infarction by antilipolytic treatment using a nicotinic-acid analogue. Lancet 1975;i:295–300.

    Google Scholar 

  23. Horgan JH, O'Callaghan WG, Teo KK. Therapy of angina pectoris with low-dose perhexiline. J Cardiovasc Pharmacol 1981;3:566–572.

    CAS  PubMed  Google Scholar 

  24. Shah RR, Oates NS, Idle JR, Smith RL, Lockhart JDF. Impaired oxidation of debrisoquine in patients with perhexiline neuropathy. BMJ 1982;284:295–299.

    CAS  PubMed  Google Scholar 

  25. Morgan MY, Reshef R, Shah RR, Oates NS, Smith RL, Sherlock S. Impaired oxidation of debrisoquine in patients with perhexiline liver injury. Gut 1984;25:1057–1064.

    CAS  PubMed  Google Scholar 

  26. Lopaschuk GD, Wall SR, Olley PM, Davies NJ. Etomoxir, a carnitine palmitoyl transferase I inhibitor, protects hearts from fatty acid-induced ischemia injury independent of changes in long chain acylcarnitine. Circ Res 1988;63:1036–1043.

    CAS  PubMed  Google Scholar 

  27. Drake-Holland AJ, Passingham JE. The effect of Oxfenicine on cardiac carbohydrate metabolism in intact dogs. Basic Res Cardiol 1983;78:19–27.

    Article  CAS  PubMed  Google Scholar 

  28. Higgins AJ, Morville M, Burges RA, Gardiner DG, Page MG, Blackburn KJ. Oxfenicine diverts rat muscle metabolism from fatty acid to carbohydrate oxidation and protects the ischemia rat heart. Life Sci 1980,27:963–970.

    Article  CAS  PubMed  Google Scholar 

  29. Pepine CJ, Wolff AA for the Ranolazine Study Group. A controlled trial with a novel anti-ischemic agent, ranolazine, in chronic stable angina pectoris that is responsive to conventional antianginal agents. Am J Cardiol 1999;84:46–50.

    CAS  PubMed  Google Scholar 

  30. Kantor PF, Lucien A, Korak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000;86:580–588.

    CAS  PubMed  Google Scholar 

  31. Sellier P. Chronic effects of trimetazidine on ergometric parameters in effort angina. Cariovasc Drugs Ther 1990;4:822–823.

    Google Scholar 

  32. Sellier P, Harpy C, Corona P, Audouin P, Ourbak P. Acute effects of trimetazidine on ergometric parameters in effort angina. Cardiovasc Drugs Ther 1990;4:820–821.

    PubMed  Google Scholar 

  33. Dalla-Volta S, Maraglino G, Della-Valentina P, Viena P, Desideri A. Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study. Cardiovasc Drugs Ther 1990;4:853–860.

    Article  PubMed  Google Scholar 

  34. Detry JM, Sellier P, Pennaforte S, Cokkinos D, Dargie H, Mathes P. Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Br J Clin Pharmacol 1994,37:279–288.

    CAS  PubMed  Google Scholar 

  35. ManchandaSC, Krischnaswami S. Combination treatment with trimetazidine and diltiazem in stable angina pectoris. Heart 1997;78:353–357.

    CAS  PubMed  Google Scholar 

  36. Stanley WC, Marzilli M. Metabolic therapy in the treatment of ischaemic heart disease: the pharmacology of trimetazidine. Fundamental and Clin Pharmacol 2003;17:133–145.

    CAS  Google Scholar 

  37. Vitale C, Wajngaten M, Sposato B, Gebara O, Rossini P, Fini M, Volterrani M, Rosano GMC. Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease. Eur Heart J 2004;25:1814–1821.

    Article  CAS  PubMed  Google Scholar 

  38. Lopaschuk GD. Optimizing cardiac energy metabolism: how can fatty acid and carbohydrate metabolism be manipulated? Cor Art Dis 2000;12:S8–S11.

    Google Scholar 

  39. Bashore TM, Magorien DJ, Letterio J, Shaffer P, Unverferth DV. Histologic and biochemical correlates of left ventricular chamber dynamics in man. J Am Col Cardiol 1987;9:734–742.

    CAS  Google Scholar 

  40. Hoppel CL, Tandler B, Parland W, Turkaly JS, Albers LD. Hamster cardiomyopathy: a defect in oxidative phosphorylation in the cardiac interfibrillar mitochondria. J Biol Chem 1982;257:1540–1548.

    CAS  PubMed  Google Scholar 

  41. Sabbah HN, Sharov VG, Riddle JM, Kono T, Lesch M, Goldstein S: Mitochondrial abnormalities in myocardium of dogs with chronic heart failure. J Mol. Cell Cardiol 1992;24:1333–1347.

    Article  CAS  PubMed  Google Scholar 

  42. Sharov VG, Sabbah HN, Cook JM, Silverman N, Lesch M, Goldstein S: Abnormal mitochondrial function in myocardium of dogs with chronic heart failure. J Mol Cell Cardiol 1998;30:1757–1762.

    Article  CAS  PubMed  Google Scholar 

  43. Stanley WC, CL Hoppel. Mitochondrial dysfunction in heart failure: potential for therapeutic interventions? Cardiovasc Res 2000;45:805–806.

    Article  CAS  PubMed  Google Scholar 

  44. Paolisso G,Gambardella A, Galzerano D, Amore AD', Rubino P, Verza M, Teasuro P, Varricchio M, Onofrio FD'. Total body and myocardial substrate oxidation in congestive heart failure. Metabolism 1994;43:174–78.

    CAS  PubMed  Google Scholar 

  45. Opie L. The heart : physiology, from cell to circulation. Philadelphia : Lippincott-Raven, 1998.

    Google Scholar 

  46. Stanley WC, Lopaschuk GD, Hall JH, McCormack JG. Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions: Potential for pharmacological interventions. Cardiovasc Res 1997;33:243–257.

    Article  CAS  PubMed  Google Scholar 

  47. Panchal AR, Stanley WC, Kerner J, Sabbah HN. Beta-receptor blockade decreases carnitine palmitoyl transferase I activity in dogs with heart failure. J Card Fail 1998;4:121–126.

    CAS  PubMed  Google Scholar 

  48. Eichhorn EJ, Heesch CM, Barnett JH, Alvarez LG, Fass SM, Grayburn PA, Hatfield BA, Marcoux LG, Malloy CR. Effects of metoprolol on myocardial function and energetics in patients with ischemic dilated cardiomyopathy: a randomized double blind, placebo-controlled study. J Am Coll Cardiol 1994;24:1310–1320.

    CAS  PubMed  Google Scholar 

  49. Mjøs OD: Effect of free fatty acids on myocardial function and oxygen consumption in intact dogs. J Clin Invest 1971;50:1386–1389.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  51. Korvald C, Elvenes OP, Myrmel T. Myocardial substrate metabolism influences left ventricular energetics in vivo. Am J Physiol 2000,278:H1345–H1351.

    CAS  Google Scholar 

  52. Bersin RM, Wolfe C, Kwasman M, Lau D, Klinski C, Tanaka K, Khorrami P, Henderson GN, de-Marco T, Chatterjee K: Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate. J Am Coll Cardiol 1994;23:1617–1624.

    CAS  PubMed  Google Scholar 

  53. Di Lisa F, Chong-Zu F, Gambassi G, Hogue GA, Kudryashova I, Hansford RG: Altered pyruvate dehydrogenase control and mitochondrial and free Ca2+ in hearts of cardiomyopathic hamsters. Am J Physiol 1993;264: H2188–H2197.

    CAS  PubMed  Google Scholar 

  54. D'hahan N, Taouil K, Dassouli A, Morel JE: Long-term therapy with trimetazidine in cardiomyopathic Syrian hamster BIO 14:6. Euro J Pharmacol. 1997;328:163– 174.

    Google Scholar 

  55. Turcani M, H Rupp. Etomoxir improves left ventricular performance of pressure-overloaded rat heart. Circulation 1997;96:3681–3686.

    CAS  PubMed  Google Scholar 

  56. Brottier L, Barat JL, Combe C, et al. Therapeutic value of a cardioprotective agent in patients with severe ischemic cardiomyopathy. Eur Heart J 1990;11:207–212.

    CAS  PubMed  Google Scholar 

  57. Belardinelli R, Purcaro A. Effects of trimetazidine on the contractile response of chronically dysfunctional myocardium to low-dose dobutamine in ischaemic cardiomyopathy. Eur Heart J 2001;22:2164–2170.

    CAS  PubMed  Google Scholar 

  58. Fragasso G, Piatti PM, Monti L, et al. Short and long-term effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy. Am Heart J 2003; 146:E18.

    Article  CAS  PubMed  Google Scholar 

  59. Rosano GMC, Vitale C, Sposato B, Mercuro G, Fini M. Trimetazidine improves left ventricular function in diabetic patients with coronary disease: a double-blind placebo-controlled study. Cardiovasc Diabet 2003;2:16–25.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan

    Hani N. Sabbah Ph.D. (Director)

  2. Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio

    William C. Stanley Ph.D.

  3. Cardiovascular Research, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202

    Hani N. Sabbah Ph.D. (Director)

Authors
  1. Hani N. Sabbah Ph.D.
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  2. William C. Stanley Ph.D.
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Corresponding author

Correspondence to Hani N. Sabbah Ph.D..

Additional information

This work was supported by a grant from the National Heart, Lung, and Blood Institute PO1 HL074237-03

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Sabbah, H.N., Stanley, W.C. Metabolic Therapy for Heart Disease: Impact of Trimetazidine. Heart Fail Rev 10, 281–288 (2005). https://doi.org/10.1007/s10741-005-7541-5

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