Ernährung & Medizin 2004; 19(3): 113-120
DOI: 10.1055/s-2004-833692
L-Carnitin

© Hippokrates Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG

Einfluss von L-Carnitin auf das Herz - Ein Mikronährstoff mit hämodynamischen und energetischen Wirkungen auf das isolierte Langendorff-Herz

L-Carnitine and the heart - a micronutrient with haemodynamic and energetic effects on the isolated Langendorff-heartHeinz Löster
Further Information

Publication History

Publication Date:
04 December 2006 (online)

Zusammenfassung

Zur Untersuchung der Wirkungen des Mikronährstoffes L-Carnitin auf das Herz wurde das Modell des isolierten Herzens nach Langendorff verwendet. Es wurde gefunden, dass nach einer Ischämieperiode von 20 min die Wiederherstellung suffizienter hämodynamischer Parameter (bes. des linksventrikulären Druckes und des Koronarflusses) und die Wiederauffüllung der ATP- bzw. CrP-Speicher der isolierten Herzen von der Perfusatzusammensetzung abhängig ist. In der Reperfusionsphase hatten höhere Na-palmitat-Konzentrationen (1,2 vs. 0,4 mmol/l), die Anwesenheit von Glucose und die Zugabe von L-Carnitin in das Perfusat eine protektive Wirkung. L-Carnitin bewirkte bei allen Perfusatzusammensetzungen eine Verbesserung der hämodynamischen Parameter, besonders bei den Herzen, die durch einen Mangel an Fettsäuren oder Glucose gekennzeichnet waren. Acetyl- und Propionyl-L-carnitin hatten gleichsinnige, aber unterschiedliche Wirkungen im Vergleich zu L-Carnitin, wobei besonders Propionyl-L-carnitin höhere und gleichmäßigere Werte brachte, verglichen mit den Kontrollen und mit L-Carnitin.

Die positiven Ergebnisse der Untersuchungen des Einflusses von L-Carnitin und seiner kurzkettigen Ester auf das Verhalten isolierter Langendorff-Herzen deuten auf eine protektive Wirkung dieser Substanzen in der Reperfusionsperiode hin.

Summary

The effects of the micronutrient L-carnitine on the heart were investigated by means of the isolated Langendorff heart model. It could be established that the composition of the perfusate influenced both the restoration of haemodynamic parameters (particularly left-ventricular pressure and coronary flow) and the replenishing of ATP and CrP stores of the isolated heart after an ischaemic period of 20 minutes. Protective effects during reperfusion were found with higher sodium palmitate concentrations (1.2 vs 0.4), the presence of glucose or the addition of L-carnitine to the perfusate. Irrespective of the composition of the perfusate, L-carnitine effected an improvement in the haemodynamic parameters, especially in fatty acid- or glucose-deficient hearts. Similar but slightly different results were achieved with acetyl and propionyl-L-carnitine. Particularly the values produced by propionyl-L-carnitine were higher and more stable than those found with L-carnitine and the controls.

The favourable results found during the investigation of the effects of L-carnitine and its short-chain esters on isolated Langendorff hearts suggests that these substances have a protective influence during reperfusion.

Literatur

  • 1 Bartels GL, Remme WJ, Pillay M. et al. . Acute improvement of cardiac function with intravenous L-propionylcarnitine in humans.  JCardiovasc Pharmacol. 1992;  20 157-164
  • 2 Bartels GL, Remme WJ, Holwerda KJ, Kruijssen DACM. Anti-ischemic efficacy of L-propionylcarnitine - a promising novel metabolic approach to ischemia?.  Eur Heart J. 1996;  17 414-420
  • 3 Bieber LL. Carnitine.  Ann Rev Biochem. 1988;  57 261-283
  • 4 Bittl JA, Ingwall JS. Intracellular high-nergy phosphate transfer in normal and hypertrophied myocardium.  Circulation. 1987;  75 96-101
  • 5 Broderick TL, Quinney HA, Lopaschuk GD. Carnitine stimulation of glucose oxidation in the fatty acid perfused isolated working heart.  J Biol Chem. 1992;  267 8162-8170
  • 6 Broderick TL, Quinney HA, Barker C, Lopaschuk GD. Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after transient period of global ischemia is accompanied by stimulation of glucose oxidation.  Circulation. 1993;  87 972-981
  • 7 Chiddo A, Gaglione A, Musci S. et al. . Hemodynamic study of intravenous propionyl-L-carnitine in patients with ischemic heart disease and normal left ventricular function.  Cardiovasc Drugs Ther. 1991;  5 107-111
  • 8 Cohen SM, Werrmann JG, King BW. Simultaneous 31P nuclear magnetic resonance spectroscopy and mechanical function in working heart models affected by drugs.  Drug Dev Res. 1989;  18 305-325
  • 9 Döring HJ. The isolated perfused heart according to Langendorff technique - function - application.  Physiol Bohemoslovaca. 1990;  39 481-504
  • 10 Ferrari R, Pasini E, Condorelli E. et al. . Effect of propionyl-L-carnitine on mechanical function of isolated rabbit heart.  Cardiovasc Drugs Ther. 1991;  5 17-23
  • 11 Ferrari R, Di F Lisa, De JW Jong. et al. . Prolonged propionyl-L-carnitine pre-treatment of rabbit: biochemical, hemodynamic and electrophysiological effects on myocardium.  J Mol Cell Cardiol. 1992;  24 219-232
  • 12 Ferrari R, De Giuli F. The propionyl-L-carnitine hypothesis: an alternative approach to treating heart failure.  J Card Fail. 1997;  3 217-224
  • 13 Finegan BA, Clanachan AS, Coulson CS, Lopaschuk GD. Adenosine modification of energy substrate use in isolated hearts perfused with fatty acids.  Am J Physiol. 1992;  262 H1501-H1507
  • 14 Ichihara K, Neely JR. Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids.  Am J Physiol. 1985;  249 H492-H497
  • 15 Ingwall JS, Kobayashi K, Bittl JA. 31P NMR magnetization transfer studies of the intact heart. In: Gupta RK (ed). NMR Spectroscopy of Cells and Organisms. Vol I. Boca Raton: CRC Press 1987: 51-68
  • 16 Johnston DJ, Liu P, Okada RD. Assessment of myocardial ischemia and infarction by magnetic resonance imaging. In: Osbakken M, Haselgrove J (eds). NMR Techniques in the Study of Cardiovascular Structure and Function. Mount Kisco, New York: Futura Publ. Comp 1988: 95-122
  • 17 Katz KM, Messineo FC. Lipid membrane interactions and the pathogenesis of ischemic damage in myocardium.  Circ Res. 1981;  48 1-16
  • 18 Kerbey AL, Randle PJ, Cooper RH. et al. . Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide.  Biochem J. 1976;  154 327-348
  • 19 Liedtke AJ. Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart.  Prog Cardiovasc Dis. 1981;  23 321-336
  • 20 Liedtke JA, De L Maison, Eggleston AM. et al. . Changes in substrate metabolism and of excess fatty acids in reperfused myocardium.  Circ Res. 1988;  62 535-562
  • 21 Löster H, Punzel M. Effects of L-carnitine on mechanical recovery of isolated rat hearts in relation to the perfusion with glucose and palmitate.  Mol Cell Biochem. 1998;  185 65-75
  • 22 Löster H, Keller T, Grommisch J, Gründer W. Effects of L-carnitine and its acetyl and propionyl esters on ATP and PCr levels of isolated rat hearts perfused without fatty acids and investigated by means of 31P-NMR spectroscopy.  Mol Cell Biochem. 1999;  200 93-102
  • 23 Löster H. Carnitine and Cardiovascular Diseases. Bochum: Ponte Press 2003
  • 24 Lopaschuk GD, Wall SR, Olley PM, Davies NJ. Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine.  Circ Res. 1988;  63 1036-1043
  • 25 Lopaschuk GD, Mc Neill GF, Mc Veigh JJ. Glucose oxidation is stimulated in reperfused hearts with the carnitine palmitoyltransferase I inhibitor, Etomoxir.  Mol Cell Biochem. 1989;  88 175-179
  • 26 Lopaschuk GD, Broderick TL, Quinney AH, Saddik M. Both carnitine and carnitine palmitoyltransferase 1 inhibitors stimulate glucose oxidation in isolated hearts perfused with high concentrations of fatty acids. In: Carter AL (ed). Current Concepts in Carnitine Research. Boca Raton: CRC Press 1992: 231-243
  • 27 Lopaschuk GD, Saddik M. The relative contribution of glucose and fatty acids to ATP production in hearts reperfused following ischemia.  Mol Cell Biochem. 1992;  116 111-116
  • 28 Lopaschuk GD, Warmbolt RB, Barr RL. An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acids during aerobic reperfusion of ischemic hearts.  J Pharmacol Exp Ther. 1993;  264 135-144
  • 29 Mickle DAG, Del PJ Nido, Wilson GJ, Harding RD, Romaschin AD. Exogenous substrate preference of the postischemic myocardium.  Cardiovasc Res. 1986;  20 256-263
  • 30 Opie LH. Role of carnitine in fatty acid metabolism of normal and ischemic myocardium.  Am Heart J. 1979;  97 375-388
  • 31 Paulson DJ, Schmidt MJ, Romens J, Shug AL. Metabolic and physiological differences between zero-flow and low-flow ischemia: effects of L-acetylcarnitine.  Basic Res Cardiol. 1984;  79 551-561
  • 32 Piper HM, Das A. Detrimental actions of endogenous fatty acids and their derivatives. A study of ischemic mitochondrial injury.  Bas Res Cardiol. 1987;  82 187-196
  • 33 Ramsay RR, Arduini A. The carnitine acyltransferases and their role in modulating acyl-CoA pools.  Arch Biochem Biophys. 1993;  302 307-314
  • 34 Regitz V, Paulson DJ, Noonan J, Fleck E, Shug AL. Protection of the ischemic myocardium by propionylcarnitine taurine amide. Comparison with other carnitine derivatives.  ZKardiol. 1987;  76 53-58
  • 35 Renström B, Liedtke JA, Nellis SH. Mechanisms of substrate preference for oxidative metabolism during early myocardial reperfusion.  Am J Physiol. 1990;  259 H317-H323
  • 36 Saddik M, Lopaschuk GD. Myocardial triglyceride turnover during reperfusion of isolated rat hearts subjected to a transient period of global ischemia.  J Biol Chem. 1992;  267 3825-3831
  • 37 Shug AL, Shrago E, Bittar N, Folts JD, Koke JR. Acyl-CoA inhibition of adenine nucleotide translocation in the ischemic myocardium.  Am J Physiol. 1975;  228 689-692
  • 38 Shug AL, Thomsen JH, Folts JD. et al. . Changes in tissue levels of carnitine and other metabolites during myocardial ischemia and anoxia.  Arch Biochem Biophys. 1978;  187 25-33
  • 39 Siliprandi N, Sartorelli L, Ciman M, Di Lisa F. Carnitine: metabolism and clinical chemistry.  Clin Chim Acta. 1989;  183 3-11
  • 40 Subramanian R, Plehn S, Nooman J. et al. . Free radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters.  Z Kardiol. 1987;  76 41-45
  • 41 Suzuki Y, Kamikawa T, Kobayashi A, Yamazaki N. Effects of L-carnitine on tissue levels of free fatty acids, acyl-CoA, and acylcarnitine in ischemic heart. In: Chazov E, Saks V, Rona G (eds.): Adv Myocardiol, Vol. 4. New York: Plenum Publ Corp 1983: 549-557
  • 42 Van Bilsen M, Engels W, Willemsen PHM. et al. . Arachidonic acid accumulation and eicosanoid synthesis during ischemia and reperfusion in isolated rat hearts.  Progr Appl Microcirc. 1987;  12 236-243
  • 43 Vick-Mo H, Mjos OD. Influence of free fatty acids on myocardial oxygen consumption in intact dogs.  Am J Cardiol. 1981;  48 361-365
  • 44 Zweier JL, Jacobus E. Substrate-induced alteration of high energy phosphate metabolism and contractile function in the perfused heart.  J Biol Chem. 1987;  262 8015-8021

PD Dr. Heinz Löster

Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik

Universität Leipzig

Liebigstraße 27

04103 Leipzig

    >