Copyright © 1994 by the European Society of Cardiology.
© 1994 The European Society of Cardiology
Metabolic effects of propionate, hexanoate and propionylcarnitine in normoxia, ischaemia and reperfusion
Does an anaplerotic substrate protect the ischaemic myocardium?
*Departments of Medical Biochemistry University of Oulu Oulu, Finland
Internal Medicine, University of Oulu Oulu, Finland
Received 6 July 1993; revised 15 December 1993; .
Correspondence: Ilmo Hassinen, MD, Associate Professor, Department of Medical Biochemistry, University of Oulu, Kajaanintie 52 A, FIN-90220 Oulu, Finland
Abstract
It has been suggested that propionyl-L-carnitine administration to iscliaemic hearts facilitates the restoration of cardiac function upon reperfusion, but it is still a matter of dispute whether its effect is conveyed via the metabolic effect of the propionyl moiety, the carnitine moiety or other mechanisms involving membrane receptor interactions. The metabolism of propionylcarnitine involves the formation of succinyl-CoA, which causes an increase in the total amount of tricarboxylic acid cycle intermediates. According to the current paradigm, anaplerosis ensures rapid restoration of tricarboxylic acid cycle activity during reperfusion.
To evaluate the contribution of anaplerosis to the protective effect of propionylcarnitine during ischaemia and reperfusion, isolated rat hearts were perfused with Krebs-Henseleit bicarbonate buffer containing 5 mM glucose+insulin (12 IUper litre), to which 1 mu propionate, 0·8 mM hexanoate or 1 mM propionylcarnitine were added Global 20 or 24 min no-flow ischaemia was followed by 10 min reperfusion. The flavoprotein redox state, myoglobin oxygenation, oxygen consumption and mechanical functioning of the heart were recorded and metabolities determined in freeze-trapped tissue. In parallel experiments, the cellular energy state was studied with phosphorus nuclear magnetic resonance spectrometry.
The addition of 1 mM propionylcarnitine failed to cause an anaplerotic effect, but did bring about an oxidation of flavins, probably due to citrate synthase inhibition. Propionate showed similar but stronger effects and a marked anaplerosis, but still failed to improve the recovery of the heart upon reperfusion. The addition of hexanoate caused marked anaplerosis upon reperfusion and flavin reduction. The results failed to demonstrate that propionylcarnitine had any beneficial effect on the ischaemic myocardium.
Key Words: Propionylcarnitine • propionate • ischaemia • reperfusion • tissue protection
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. C. Okere, T. A. McElfresh, D. Z. Brunengraber, W. Martini, J. P. Sterk, H. Huang, M. P. Chandler, H. Brunengraber, and W. C. Stanley Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion J Appl Physiol, January 1, 2006; 100(1): 76 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Comte, G. Vincent, B. Bouchard, M. Jette, S. Cordeau, and C. D. Rosiers A 13C Mass Isotopomer Study of Anaplerotic Pyruvate Carboxylation in Perfused Rat Hearts J. Biol. Chem., October 17, 1997; 272(42): 26125 - 26131. [Abstract] [Full Text] [PDF]
|
|