Skip to main content
SpringerLink
Log in

Protection of the ischemic diabetic heart by L-propionylcarnitine therapy

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Diabetics suffer from an increased incidence of myocardial infarction and are less likely to survive an ischemic insult. Since L-propionylcarnitine (LPC) has been shown to protect against ischemic/reperfusion injury, we hypothesized that LPC may be of even greater benefit to the diabetic heart. Diabetes was induced by i.v. streptozotocin, 60 mg/kg; duration: 12 wks. The chronic effect of LPC was determined by daily i.p. injections (100 mg/kg) for 8 wks. The acute effects of LPC were determined by adding it to the perfusion medium (5 mM) of control and diabetic hearts. Initial cardiac contractile performance of isolated perfused working hearts was assessed by varying left atrial filling pressure. Hearts were then subjected to 90 min of low flow global ischemia followed by 30 min reperfusion. Chronic LPC treatment had no effect on initial cardiac performance in either control or diabetic hearts. Acute addition of LPC to the perfusion medium enhanced pump performance of control hearts, but had no effect in diabetic hearts. Both acute and chronic LPC significantly improved the ability of control and diabetic hearts to recover cardiac contractile performance after ischemia and reperfusion, however, chronic treatment was more effective in diabetic hearts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barrett-Connor EL, Cohn BA, Wingard DL, Edelstein SL: Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study. JAMA 265: 627–631, 1991

    Google Scholar 

  2. Assmann G, Schulte H: Diabetes mellitus and hypertension in the elderly: Concomitant hyperlipidemia and coronary heart disease risk. Am J Cardiol 63: 33H-37H, 1989

    Google Scholar 

  3. Henning R, Lundman T: Swedish cooperative CCV study: a study of 2009 patients with acute myocardial infarction from twelve Swedish hospitals with coronary care units. I: A description of the early stage. ACTA Med Scand 198: 1–64, 1975

    Google Scholar 

  4. Kotler TS, Diamond GA: Myocardial ischemia in diabetic patients. Ann Intern Med 109: 678–678, 1988

    Google Scholar 

  5. Kannel WB: Role of diabetes in cardiac disease: conclusions from population studies. In: S Zonaraich (ed.) Diabetes and the Heart. Thomas, Springfield, IL, 1978, pp. 97–112

    Google Scholar 

  6. Hearse DJ, Steward DA, Green DG: Diabetes and the survival and recovery of the anoxic myocardium. J Mol Cell Cardiol 7: 397–415, 1975

    Google Scholar 

  7. Hearse DJ, Steward DA, Green DG: Myocardial susceptibility to ischemic damage: a comparative study of disease models of rats. Eur J Cardiol 75: 437–450, 1978

    Google Scholar 

  8. Ingebretsen CG, Moreau P, Hawelu-Johnson C, Ingebretsen WR: Performance of diabetic rat hearts: effects of anoxia and increased work. Am J Physiol 239: H614-H620, 1980

    Google Scholar 

  9. Paulson DJ, Kopp SJ, Peace DG, Tow JP: Improved postischemic recovery of cardiac pump function in exercised trained diabetic rats. J Appl Physiol 65: 187–193, 1988

    Google Scholar 

  10. Pieper GM, Gross GJ: Diabetes alters postischemic response to a prostacyclin mimetic. Am J Physiol 256: H1353-H1360, 1989

    Google Scholar 

  11. Feuvray D, Idell-Wenger JA, Neely JR: Effects of ischemia on rat myocardial function and metabolism in diabetes. Am J Physiol 44: 322–329, 1979

    Google Scholar 

  12. Khandoudi N, Bernard M, Cozzone PA, Feuvray D: Intracellular pH and role of Na/H exchange during ischaemia and reperfusion on normal and diabetic rat hearts. Cardiovasc Res 24: 873–878, 1980

    Google Scholar 

  13. Tani M, Neely JR: Hearts from diabetic rats are more resistant toin vitro ischemia: possible role of altered calcium metabolism. Circ Res 62: 931–940, 1988

    Google Scholar 

  14. Paulson DJ, Traxler J, Schmidt 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 and fatty acid oxidation. Cardiovasc Res 20: 536–541, 1986

    Google Scholar 

  15. Liedtke AJ, DeMaison L, Nellis SH: Effects of L-propionylcarnitine on mechanical recovery during reflow in intact hearts. Am J Physiol 255: H169-H176, 1988

    Google Scholar 

  16. Ferrari R, Ceconi C, Curello S, Pasini E, Visioli O: Protective effect of propionyl-L-carnitine against ischaemia and reperfusion-damage. Mol Cell Biochem 88: 161–168, 1989

    Google Scholar 

  17. Di Lisa F, Menabò R, Siliprandi N: L-Propionyl-carnitine protection of mitochondria in ischemic rat hearts. Mol Cell Biochem 88: 169–173, 1989

    Google Scholar 

  18. Leasure JE, Kordenat K: Effect of propionyl-L-carnitine on experimental myocardial infarction in dogs. Cardiovasc Drugs Ther 5 Suppl 1: 85–96, 1991

    Google Scholar 

  19. Aomine M, Nobe S, Arita M: Electrophysiologic effects of a short-chain acyl carnitine, L-propionylcarnitine, on isolated canine Purkinje fibers. J Cardiovasc Pharmacol 13: 494–501, 1989

    Google Scholar 

  20. Aomine M, Arita M: Differential effects of L-propionylcarnitine on the electrical and mechanical properties of Guinea pig ventricular muscle in normal and acidic conditions. J Electrocardiol 20: 287–296, 1987

    Google Scholar 

  21. Aomine M, Arita M, Shimada T: Effects of L-propionylcarnitine on electrical and mechanical alterations induced by amphiphilic lipids in isolated Guinea pig ventricular muscle. Heart Vessel 4: 197–206, 1988

    Google Scholar 

  22. Di Biase M, Tritto M, Pitzalis MV, Favale S, Rizzon P: Electrophysiological evaluation of intravenous L-propionylcarnitine in man. Int J Cardiol 30: 329–333, 1991

    Google Scholar 

  23. Siliprandi N, Di Lisa F, Menabò R: Propionyl-L-carnitine: Biochemical significance and possible role in cardiac metabolism. Cardiovasc Drugs Ther 5 Suppl 1: 11–16, 1991

    Google Scholar 

  24. Hülsmann WC: Biochemical profile of propionyl-L-carnitine. Cardiovasc Drugs Ther 5 Suppl 1: 7–10, 1991

    Google Scholar 

  25. Wall SR, Lopaschuk GD: Glucose oxidation rates in fatty acidperfused isolated working hearts from diabetic rats. Biochim Biophys Acta 1006: 97–103, 1989

    Google Scholar 

  26. Vary TC, Neely JC: A mechanism for reduced myocardial carnitine levels in diabetic animals. Am J Physiol 243: H154-H158, 1982

    Google Scholar 

  27. Shug A, Paulson D, Subramanian R, Regitz V: Protective effects of propionyl-L-carnitine during ischemia and reperfusion. Cardiovasc Drugs Ther 5 Suppl 1: 77–84, 1991

    Google Scholar 

  28. Packer L, Valenza M, Serbinova E, Starke-Reed P, Frost K, Kagan V: Free radical scavenging is involved in the protective effect of L-propionyl-carnitine against ischemia-reperfusion injury of the heart. Arch Biochem Biophys 288: 533–537, 1991

    Google Scholar 

  29. Randle PJ: Fuel selection in animals. Biochem Soc Trans 14: 799–806, 1986

    Google Scholar 

  30. Paulson DJ, Schmidt MJ, Traxler JS, Ramacci MT, Shug AL: Improvement of myocardial function in diabetic rats after treatment with L-carnitine. Metabolism 33: 358–363, 1984

    Google Scholar 

  31. Paulson DJ, Kopp SJ, Peace DG, Tow JP: Myocardial adaptation to endurance exercise training in diabetic rats. Am J Physiol 252: R1073-R1081, 1987

    Google Scholar 

  32. Pierce GN, Ramjiawan B, Dhalla NS, Ferrari R: Na1-H+ exchange in cardiac sarcolemmal vesicles isolated from diabetic rats. Am J Physiol 258: H255-H261, 1990

    Google Scholar 

Download references

Author information

Author notes

  1. Austin L. Shug

    Present address: Department of Neurology, University of Wisconsin, 33705, Madison, WI, USA

Authors and Affiliations

  1. Department of Physiology, Chicago College of Osteopathic Medicine, 555 31st Street, 60515, Downers Grove, Illinois, USA

    Dennis J. Paulson, Austin L. Shug & Jiansheng Zhao

Authors
  1. Dennis J. Paulson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Austin L. Shug
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiansheng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paulson, D.J., Shug, A.L. & Zhao, J. Protection of the ischemic diabetic heart by L-propionylcarnitine therapy. Mol Cell Biochem 116, 131–137 (1992). https://doi.org/10.1007/BF01270580

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01270580

Keywords

Search

Navigation