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Acute and Chronic Effects of Propionyl-L-Carnitine on the Hemodynamics, Exercise Capacity, and Hormones in Patients with Congestive Heart Failure

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Abstract

Carnitine is an important cofactor in the intermediary metabolism of the heart, and carnitine deficiency is associated with congestive heart failure. We therefore studied the effects of acute (IV bolus, 30 mg/kg body weight) and chronic administration (1.5 mg/d for 1 month) of propionyl-L-carnitine on hemodynamics, hormone levels, ventricular function, exercise capacity, and peak oxygen consumption in 30 patients with chronic congestive heart failure (NYHA II–III, mean EF 29.5 ± 7%) in a phase II, parallel, single-blind, randomized, and placebo-controlled study. Acute administration of propionyl-L-carnitine caused a significant reduction in pulmonary artery and pulmonary wedge pressures at both day 1 (P < 0.001) and day 30 (P < 0.05) of the study but no other hemodynamics changes. Hormone levels did not change following acute administration of the drug. Chronic administration of propionyl-L-carnitine increased peak oxygen consumption by 45% (from 16.0 ± 3 to 23.5 ± 2 mL/kg/min, P ± 0.001), exercise time by 21% (from 8.1 ± 0.5 to 9.8 ± 0.4 minutes, P < 0.01), and peak exercise heart rate by 12% (P < 0.01). These changes were concomitant with a reduction of pulmonary artery pressure. In the treated group, there was a slight, but significant (P < 0.01), reduction in left ventricular dimensions. Hemodynamics and hormones measured after 1 month of oral therapy remained unchanged, except for a fall in pulmonary artery pressures, with a nonsignificant trend towards a fall in filling pressures and plasma norepinephrine. The chronic changes in the propionyl-L-carnitine group were seen at 15 days of treatment, and no further changes in these parameters were seen at 1 month. We conclude that propionyl-L-carnitine increases exercise capacity and reduces ventricular size in patients with congestive heart failure. The drug has no significant effects on hemodynamics or neurohormone levels. The use of a single-blind design reduces the impact of the positive finding on exercise capacity.

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References

  1. Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation 1990; 82:1730-1736.

    Google Scholar 

  2. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic heart failure. N Engl J Med 1991;325: 303-310.

    Google Scholar 

  3. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302.

    Google Scholar 

  4. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE investigators. N Engl J Med 1992;327:669-677.

    Google Scholar 

  5. Ziesche S, Cobb FR, Cohn JN, Johnson G, Tristani F. Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V-HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation 1993;87(Suppl.): VI56-VI64.

    Google Scholar 

  6. Poole Wilson PA, Ferrari R. Role of skeletal muscle in the syndrome of chronic heart failure. J Mol Cell Cardiol 1996;28:2275-2285.

    Google Scholar 

  7. Siliprandi N, Di Lisa F, Pieralisi G, Ripari P, Maccari F, Menabo' R, Giamberardino MA, Vecchiet L. Metabolic changes induced by maximal exercise in human subjects following L-carnitine administration. Biochem Biophys Acta 1990;1034:17-21.

    Google Scholar 

  8. Bremer J. Carnitine-metabolism and functions. Physiol Rev 1983;63:1420-1480.

    Google Scholar 

  9. Cherchi A, Lai C, Angelino F, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: A multicenter, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharmacol Ther Toxicol 1985;23:569-572.

    Google Scholar 

  10. Brevetti G, Chiariello M, Ferulano G, et al. Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: A double-blind, cross-over study. Circulation 1988;77:767-783.

    Google Scholar 

  11. Tripp ME, Katcher ML, Peters HA, et al. Systemic carnitine deficiency presenting as familiar endocardial fibroelastosis. A treatable cardiomyopathy. N Engl J Med 1980;305: 385-390.

    Google Scholar 

  12. Waber LJ, Valle D, Neill C, Di Mauro S, Shug A. Carnitine deficiency presenting as familial cardiomyopathy: A treatable defect in carnitine transport. J Pediatr 1982;101: 700-705.

    Google Scholar 

  13. Suzuki Y, Masumuro Y, Kobayashi A, Yamazaki L, Harada Y, Osawa M. Myocardial carnitine deficiency in congestive heart failure. Lancet 1982;1:116.

    Google Scholar 

  14. Regitz V, Shug AL, Fleck E. Defective myocardial metabolism in congestive heart failure secondary to dilated cardiomyopathy and to coronary, hypertensive and valvular heart disease. Am J Cardiol 1990;65:755-760.

    Google Scholar 

  15. Regitz V, Shug AL, Schuler S, Yankah AC, Hetze R. Herzinsuffi cienz bei dilatativer kardiomyopathie und koronarer herzerkrankung-beitrag biochemischer parameter zur beurteilung der prognose. Dtsch MedWochenscher 1988;113: 781-786.

    Google Scholar 

  16. Regitz V, Muller M, Schuler S, Yankah CA, Heyzer R, Shug AL, Fleck E. Carnitinstoffwechsel-veranduregen in endetadium der dilatativen kardiomyopathie und der ischamischen herzmuskeler-krankung. Kardiologie 1987;76:1-8.

    Google Scholar 

  17. Figueiredo Ramos ACM, Elian PRP, Barrucand L, Da Silva JAF. The protective effect of carnitine in human diptheric myocarditis. Pediatr Res 1984;18:815-819.

    Google Scholar 

  18. De Leonardis V, Neri B, Baculli S, Cinelli P. Reduction cardiac toxicity of anthracyclines by L-carnitine: Preliminary overview of clinical data. Int J Clin Pharmacol Res 1985; 5:137-142.

    Google Scholar 

  19. Mancini M, Rango FC, Lincetti M, Sorrentino GP, Nolfe G. Controlled study on the therapeutic efficacy on propionyl-L-carnitine in patients with congestive heart failure. Arzneim Htelforschung 1992;42(II):1101-1104.

    Google Scholar 

  20. Caponnetto S, Canale C, Masperone MA, Terracchini V, Valentini G, Brunelli C. Efficacy of L-propionyl-carnitine treatment in patients with left ventricular dysfunction. Eur Heart J 1994;15:1267-1273.

    Google Scholar 

  21. Paulson DJ, Traxler J, Shmidt M, Noonan J, Shug AL. Protection of the ischaemic myocardium by L-propionylcarnitine: Effects on the recovery of cardiac output after ischaemia and reperfusion, carnitine transport on fatty acid oxidation. Cardiovasc Res 1986;20:536-541.

    Google Scholar 

  22. Siliprandi N, Di Lisa F, Pivetta A, Miotto G. Siliprandi D. Transport and function of L-carnitine and L-propionylcarnitine relevance to some cardiomyopathies and cardiac ischaemia. Z Kardiol 1987;76:34-40.

    Google Scholar 

  23. Tassani V, Cattapan L, Magnanimi L, Peschechera A. Anaplerotic effect of propionyl-L-carnitine in rat heart mitochondria. Biochem Biophys Res Comm 1994;199:949-953.

    Google Scholar 

  24. Di Lisa F, Menabo R, Siliprandi N. L-propionyl-carnitine protection of mitochondria in ischemic rat hearts. Mol Cell Biochem 1989;88:169-173.

    Google Scholar 

  25. Ferrari R, Di Lisa F, de Jong JW, et al. Prolonged propionyl-L-carnitine pretreatment of rabbit: Biochemical hemodynamic and electrophysiological effects on myocardium. J Mol Cell Cardiol 1992;24:219-232.

    Google Scholar 

  26. Yang XP, Samaja M, English E, et al. Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with pressure-overload cardiac hypertrophy. J Cardiovasc Pharmacol 1992;20:88-98.

    Google Scholar 

  27. Micheletti R, Giacalone G, Reggiani C, Canepari M, Bianchi G. Effect of propionyl-L-carnitine treatment on mechanical properties of papillary muscles from pressure overloaded muscle. J Mol Cell Cardiol 1992;24:41-49.

    Google Scholar 

  28. Micheletti R, Di Paola ED, Schiavone A, et al. Propionyl-L-carnitine limits chronic ventricular dilation after myocardial infarction in rats. Am J Physiol 1993;264:H111-H117.

    Google Scholar 

  29. Anand IS, Ferrari R, Kalra GS, Wahi PL, Poole-Wilson PA, Harris PC. Edema of cardiac origin: Studies of body water and sodium, renal function, hemodynamic indices, and plasma hormones in untreated congestive cardiac failure. Circulation 1989;80:299-305.

    Google Scholar 

  30. Ferrari R, Ceconi C, Signorini C, Anand IS, Harris P, Albertini A. Sample treatment for long distance air transport of human plasma hormone assay. Clin Chem 1989;35: 331-332.

    Google Scholar 

  31. Ferrari R, Ceconi C, Rodella A, Harris P, Visioli O. Hormonal response in untreated myocardial infarction. Cardioscience 1990;1:55-61.

    Google Scholar 

  32. Poiesi C, Rodella A, Mantero G, Cannella G, Ferrari R, Albertini A. Improved radioimmunoassay of atrial natriuretic peptide in plasma. Clin Chem 1989;35:1431-1434.

    Google Scholar 

  33. Ferrari R, Pasini E, Condorelli E, Cargnoni A, De Giuli F, Visioli O. Effect of propionyl-L-carnitine on mechanical function of isolated and perfused hearts. Cardiovasc Drugs Ther 1991;5:109-115.

    Google Scholar 

  34. Cevese A, Schena F, Cerutti G. Short term hemodynamic effects of intravenous propionyl-L-carnitine in anesthethized dogs. Cardiovasc Drugs Ther 1991;5:137-148.

    Google Scholar 

  35. Chiddo A, Cagione A, Musci S, Troito G, Crimaldi N, Locuratolo N, Rizzon P. Haemodynamic studies in patients with coronary artery disease and normal left ventricular function. Cardiovasc Drugs Ther 1991;5:107-112.

    Google Scholar 

  36. Bartels L. Effects of L-propionyl-carnitine on ischemia-induced myocardial dysfunction in men with angina pectoris. Am J Cardiol 1994;74:125-130.

    Google Scholar 

  37. Chiddo A, Mussi F, Bordone A, Troito G, Locuratolo N, Caglione A, Rizzon P. Effetti emodinamici e sul circolo coronarico della propionyl-L-carnitina. Cardiologia 1989;34: 111-117.

    Google Scholar 

  38. Packer M. Neurohormonal interactions and adaptations in congestive heart failure. Circulation 1988;77:721-730.

    Google Scholar 

  39. Anand IS, Kalra GS, Harris P, Poole Wilson PA, Panzali A, de Giuli F, Ferrari R., Diuretics as initial and sole treatment in chronic cardiac failure. Cardioscience 1991;2:273-278.

    Google Scholar 

  40. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311:819-823.

    Google Scholar 

  41. Packer M. The neurohumoral hypothesis: A theory to explain the mechanism of disease progression in heart failure [editorial]. J Am Coll Cardiol 1992;20:248-254.

    Google Scholar 

  42. Wilson JR, Mancini DM. Factors contributing to the exercise limitation of heart failure. J Am Coll Card 1993;4: 93A-98A.

    Google Scholar 

  43. Franciosa JA, Park M, Levine TB. Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 1981;47: 33-39.

    Google Scholar 

  44. Wilson JR, Martin JL, Schwartz D, Ferra N. Exercise intolerance in patients with congestive heart failure: Role of impaired skeletal muscles nutritive flow. Circulation 1984; 69:1079-1087.

    Google Scholar 

  45. Lipkin DP, Canepa-Anson R, Stephens MR, Poole-Wilson PA. Factors determining symptoms in heart failure: Comparison of fast and slow exercise tests. Br Heart J 1986;55: 439-445.

    Google Scholar 

  46. Drexler H, Banhardt M, Meinertz T, Wollschalager H, Lehmann M, Just H. Contrasting peripheral short term and long term efforts of converting enzyme inhibition in patients with congestive heart failure. Circulation 1989;79:491-502.

    Google Scholar 

  47. Wilson JR, Mancini DM. The mechanism of exertional fatigue in heart failure. Cardioscience 1990;1:13-19.

    Google Scholar 

  48. Wilson JR, Fink L, Maris J, Ferraro N, Power-Vanwart J, Eleff S, Change B. Evaluation of skeletal muscle energy metabolism in patients with heart failure using gated phosphorous-31 nuclear magnetic resonance. Circulation 1985; 71:57-62.

    Google Scholar 

  49. Mancini DM, Ferraro N, Tuchler M, Change B, Wilson JR. Detection of abnormal calf muscle metabolism in patients with heart failure using phosphorous-31 nuclear magnetic resonance. Am J Cardiol 1988;62:1234-1240.

    Google Scholar 

  50. Drexler H, Riede U, Schafer HE, Just H. Reduced oxidative capacity of skeletal muscles in patients with severe heart failure. Circulation 1987;76(Suppl. IV):178.

    Google Scholar 

  51. Ferrari R, Cargnoni A, de Giuli F, Pasini E, Anand IS, Visioli O. Propionyl-L-carnitine improves skeletal muscle metabolism and exercise capacity of patients with congestive heart failure (abst). Circulation 1993;88:I414.

    Google Scholar 

  52. Siliprandi N. L-Carnitine. Lancet 1990;335:1215.

    Google Scholar 

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Anand, I., Chandrashekhan, Y., De Giuli, F. et al. Acute and Chronic Effects of Propionyl-L-Carnitine on the Hemodynamics, Exercise Capacity, and Hormones in Patients with Congestive Heart Failure. Cardiovasc Drugs Ther 12, 291–299 (1998). https://doi.org/10.1023/A:1007721917561

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