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Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts

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Abstract

The mechanisms of the adverse effects of free fatty acids on the ischemic-reperfused myocardium are not fully understood. Long-chain fatty acids, including palmitate, uncouple oxidative phosphorylation and should therefore promote the formation of oxygen-derived free radicals, with consequent adverse effects. Conversely, the antianginal agent trimetazidine (TMZ), known to inhibit cardiac fatty acid oxidation, could hypothetically lessen the formation of reactive oxygen species (ROS) and thus improve reperfusion mechanical function. Isolated perfused rat hearts underwent 30 min of total global ischemia followed by 30 min of reperfusion. Hearts were perfused with glucose 5.5 mmol/l or palmitate 1.5 mmol/l with or without TMZ (100 μmol/l). Ascorbyl free radical (AFR) release during perfusion periods was measured by electron spin resonance as a marker of oxidative stress. Post-ischemic recovery in the palmitate group of heart was lower than in the glucose group with a marked rise in diastolic tension and reduction in left ventricular developed pressure (Glucose: 85 ± 11 mmHg; Palmitate: 10 ± 6 mmHg; p < 0.001). TMZ decreased diastolic tension in both glucose- and in palmitate-perfused hearts. Release of AFR within the first minute of reperfusion was greater in palmitate-perfused hearts and in hearts perfused with either substrate, this marker of oxidative stress was decreased by TMZ (expressed in arbitrary units/ml; respectively: 8.49 ± 1.24 vs. 1.06 ± 0.70 p < 0.05; 12.47 ± 2.49 vs. 3.37 ± 1.29 p < 0.05). Palmitate increased the formation of ROS and reperfusion contracture. TMZ, a potential inhibitor of palmitate-induced mitochondrial uncoupling, decreased the formation of free radicals and improved postischemic mechanical dysfunction. The novel conclusion is that adverse effects of fatty acids on ischemic-reperfusion injury may be mediated, at least in part, by oxygen-derived free radicals.

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Authors and Affiliations

  1. Faculties of Medicine and Pharmacy, IFR 100, Dijon, France

    Ségolène Gambert, Catherine Vergely, Daniel Moreau & Luc Rochette

  2. INSERM U517, EPHE, IFR 100, Dijon, France

    Rodolphe Filomenko & Ali Bettaieb

  3. Hatter Institute, Cape Heart Centre, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

    Lionel H. Opie

  4. Laboratory of Cardiovascular and Experimental Physiopathology and Pharmacology Faculties of Medicine and Pharmacy, IFR No. 100, 7, Boulevard Jeanne d'Arc, BP 87900, Dijon, 21079, France

    Luc Rochette

Authors
  1. Ségolène Gambert
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  2. Catherine Vergely
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  3. Rodolphe Filomenko
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  4. Daniel Moreau
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  5. Ali Bettaieb
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  6. Lionel H. Opie
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  7. Luc Rochette
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Correspondence to Luc Rochette.

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Gambert, S., Vergely, C., Filomenko, R. et al. Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts. Mol Cell Biochem 283, 147–152 (2006). https://doi.org/10.1007/s11010-006-2518-9

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  • DOI: https://doi.org/10.1007/s11010-006-2518-9

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