Control of Oxidative Metabolism in Volume-Overloaded Rat Hearts

Effect of Pretreatment with Propionyl-L-Carnitine
  • J. Moravec
  • Z. El Alaoui-Talibi
  • M. Moravec
  • A. Guendouz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 388)


Chronic mechanic overloading of the heart has been shown to lead to a significant depletion of tissue carnitine (1,2) that is possibly related to impaired carnitine transport to the myocardium (3, 4). At the same time, the ability of chronically overloaded hearts to oxidize exogenous palmitate is diminished (5, 6). This decrease of long-chain fatty acid utilization is accompanied by reduced myocardial oxygen consumption (MVO2) and gives rise to an impaired mechanical activity during in vitro perfusions (6, 7). Most of the above quoted alterations disappear when exogenous palmitate is replaced by octanoate, a short-chain fatty acid that has free access to mitochondrial matrix (8). This suggests that the respiratory chain of volume-overloaded rat hearts perfused in presence of long-chain fatty acids may be actually substrate limited (7). In this work, we tried to improve NADH delivery to respiratory chain by a prolonged treatment of volume-overloaded rats with millimolar concentrations of propionyl-L-carnitine (9). It has been shown that the administration of this compound significantly increases both blood plasma concentrations and myocardial tissue levels of L-carnitine (10, 11). This, in turn, may improve long chain fatty acid utilization (5) and glucose oxidation (12) via a decreased acetyl-CoA/CoA ratio (13, 14). The control and volume-overloaded hearts were perfused with 11 mM glucose and 1.2 mM palmitate (2.4 mM octanoate) over a range of left ventricular work loads, leading to a progressive increase in the myocardial V02 (7). The respective relationships between the rates of oxidative phosphorylation and different intracellular energy parameters ((cytosolic phosphorylation potential (ATP/ADPf.Pi), ADPf, and mitochondrial NAD+/NADH ratio)) as obtained in control and volume-overloaded hearts were compared for each metabolic condition examined. The effects of the pretreatment with propionyl-L-carnitine on the kinetics of oxidative phosphorylation were tested under conditions of a high work load (heart ejecting against an increased aortic resistance related to the clamp of the aortic outflow line) as described previously (6, 7).


Glucose Oxidation Myocardial Oxygen Consumption Control Heart Fatty Acid Utilization Palmitate Oxidation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Reibel DK, Uboh CE and Kent RL. (1983) Altered CoA and carnitine metabolism in pressure overloaded hypertrophied hearts. Am. J. Physiol. 244: H839–H843.PubMedGoogle Scholar
  2. 2.
    Bowé C, Nzonzi J, Corsin A, MoravecJ, and Feuvray D. (1984) Lipid intermediates in chronically volume-overloaded rat hearts. Pflügers Arch. 402: 317–320.PubMedCrossRefGoogle Scholar
  3. 3.
    Reibel DK, O’Rourke V and Forster KA. (1987) Mechanism for altered carnitine content in hypertrophied rat heart. Am. J. Physiol. 252: H561–H565.PubMedGoogle Scholar
  4. 4.
    El Alaoui-Talibi Z and Moravec J. (1989) Carnitine transport and exogenous palmitate oxidation in chronically volume-overloaded rat hearts. BBA 1003: 109–114.PubMedGoogle Scholar
  5. 5.
    Wittels B and Spann JF. (1968) Defective lipid metabolism in the failing heart. J. Clin. Invest. 47: 1787–1794.PubMedCrossRefGoogle Scholar
  6. El Alaoui-Talibi Z, Landormy S, Loireau A and Moravec J. (1992) Fatty acid oxidation and mechanical performance of volume-overloaded rat hearts. Am. J. Physiol. 262: HI068–1074.Google Scholar
  7. 7.
    Ben Cheikh R, Guendouz A and Moravec J. (1994) Control of oxidative metabolism in volume overloaded rat hearts: effect of different lipid substrates. Am. J. Physiol. 266: H2090–H2097.PubMedGoogle Scholar
  8. 8.
    Fritz IB, Kaplan E and Yue KTN. (1962) Specificity of carnitine action in fatty acid oxidation by heart muscle. Am. J. Physiol. 202: 117–121.PubMedGoogle Scholar
  9. 9.
    Ferrari R, Di Lisa F, de Jong JW, Ceconi C, Pasini E, Barbato R, Menabò R, Barbieri M, Carbai E and Mugelli A. (1992) Prolonged PLC pretreatment of rabbits: biocemical and electro- physiological effects on myocardium. J. Mol. Cell. Cardiol. 24: 219–232.PubMedCrossRefGoogle Scholar
  10. 10.
    Ferrari R, Pasini E, Condorelli E, Boraso A, Lisciani R, Marzo A, and Vision O. (1991) Effect of propionyl-L-carnitine on mechanical function of isolated rabbit heart. Cardiovasc. Drugs Ther. 5: 17–24.PubMedCrossRefGoogle Scholar
  11. 11.
    El Alaoui-Talibi Z and Moravec J. (1993) Assessment of the cardiostimulant action of propionyl-L-carnitine on chronically volume-overloaded rat hearts. Cardiovasc. Drugs Ther. 7: 357–363.PubMedCrossRefGoogle Scholar
  12. 12.
    Broderick TL, Quinney HA and Lopaschik GD. (1992) Carnitine stimulation of glucose oxidation in the fatty acids perfused isolated working hearts. J. Biol. Chem. 267: 3758–3763.PubMedGoogle Scholar
  13. 13.
    Siliprandi N, Di Lisa F, Menabò R. (1991) Propionyl-L-carnitine: biochemical significance and possible role in cardiac metabolism. Cardiovasc. Drugs Ther. 5 (suppl 1): 11–16.PubMedCrossRefGoogle Scholar
  14. 14.
    Hülsmann WC. (1991) Biochemical profile of propionyl-L-carnitine. Cardiovasc. Drugs Ther. 5 (suppl 1): 7–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Lopaschuk GD and Spafford GD. (1991) Glucose and palmitate oxidation during reperfusion of hearts from diabetic rats. In: Nagano M and Dhalla NS (eds) The diabetic Heart, Raven, NY, pp 451–464.Google Scholar
  16. 16.
    Neely JR, Whitmer KM and Mochizuki S. (1976) Effect of mechanical activity and hormones on myocardial glucose and fatty acids utilization. Circ. Res. 38 (suppl I): 122–130.Google Scholar
  17. 17.
    Williamson JR and Corkey B. (1969) Assays of intermediates of citric acid cycle and related compounds. In: Colowick SP and Kaplan NO (eds) Methods in Enzymol., Academic, NY, vol. 13, pp 439–513.Google Scholar
  18. 18.
    Staraes JW, Wilson DF and Erecinska M. (1985) Substrate dependance of metabolic state and coronary flow in perfused rat hearts. Am. J. Physiol. 249: H799–H806.Google Scholar
  19. 19.
    Lawson JW and Veech RL. (1979) Effects of pH and free Mg++ on Keq of the creatine kinase and other phosphate hydrolases and phosphate transfer reactions. J. Biol. Chem. 254: 6528–6537.PubMedGoogle Scholar
  20. 20.
    Nuuntinen H, Hiltunen JK and Hassinen IE. (1981) The glutamate deshydrogense system and redox state of mitochondrial free NAD in myocardium. FEBS Letter 128: 356–360.CrossRefGoogle Scholar
  21. 21.
    Bishop SP and Altschuld RA. (1970) Increased glycolytic metabolism in cardiac hypertrophy and congestive heart failure. Am. J. Physiol. 218: 153–159.PubMedGoogle Scholar
  22. 22.
    Shug A, Paulson D, Subramanian R and Regitz V. (1991) Protective effects of propionyl-L-carnitine during ischemia and reperfusion. Cardiovasc. Drugs Ther. 5 (suppl 1): 77–84.PubMedCrossRefGoogle Scholar
  23. 23.
    Mc Cormack JG, Halestrap AP and Denton RM. (1990) Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol. Rev. 70: 391–425.Google Scholar

Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • J. Moravec
    • 1
  • Z. El Alaoui-Talibi
    • 1
  • M. Moravec
    • 1
  • A. Guendouz
    • 1
  1. 1.Laboratoire d’Energétique et de Cardiologie CellulaireFaculté de PharmacieDijonFrance

Personalised recommendations