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Cardiovascular Research 1995 30(5):648-655; doi:10.1016/S0008-6363(95)00075-5
© 1995 by European Society of Cardiology
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Copyright © 1995, European Society of Cardiology

Nature of the cardiomyocyte injury induced by lipid hydroperoxides

Catherine Thollon*, Jean Pierre Iliou, Christine Cambarrat, Frédéric Robin and Jean Paul Vilaine

Division Pathologies Cardiaques et Vasculaires, Institut de Recherches Servier, 11, rue des Moulineaux, 92150 Suresnes, France

* Corresponding author. Tel. (+33)-1-41-18-23-41; Fax (+33)-1-41-18-24-30.

Objective: As a result of oxidative stress to membrane lipid matrix, the peroxidation of polyunsaturated fatty acids induced the transient formation of lipid hydroperoxides (ROOM). The aim of this study was to evaluate the damaging effects of ROOH on the cardiac cell and the link between the alterations observed and intracellular calcium overload. Methods: Necrosis of cultured rat cardiac cells was determined by measuring the release of lactate dehydrogenase (LDH). In guinea-pig papillary muscles, action potential (AP) and isometric tension were recorded with standard microelectrodes and a transducer, respectively. The reactive oxygen species (ROS) scavenging properties of tested compounds were determined using a cell-free model of lipid photoperoxidation. Results: 15(S)-HpETE (15(S)-hydroperoxyeicosatetraenoic acid), an arachidonic acid hydroperoxide, induced a concentration-dependent loss of cardiomyocytes membrane integrity. The release of LDH induced by 15(S)-HpETE (30 µM) was prevented by a ROS scavenger, BW755C (10 µM), but not by a sarcolemmal calcium channel blocker, Amlodipine (10 µM), or a calcium overload protective agent, R56865 [GenBank] (10 µM). Cardiomyocytes necrosis induced by calcium paradox was prevented by Amlodipine (10 µM) and R56865 [GenBank] (10 µM), but not by BW755C (10 µM). Superfusion of papillary muscles with 15(S)-HpETE (20 µM) induced a membrane depolarization and a marked reduction in the AP amplitude and duration. Concomitantly, a transient positive inotropic effect and a progressive rise in diastolic tension were observed. These alterations were maximal after 15 min and associated with delayed after-depolarizations (DADs) and after-contractions. Every alteration was inhibited by BW755C (10 µM) and R56865 [GenBank] (30 µM), but not by Amlodipine (1 µM). Ryanodine (1 µM), a blocker of sarcoplasmic reticulum calcium channel, only prevented the appearance of DADs and after-contractions. Only BW755C exibited ROS scavenging properties. Conclusions: ROOH induced enzyme leakage and electromechanical alterations in cardiac cells. These effects of ROOH implicated oxidative mechanisms and resulted in an intracellular calcium overload.

KEYWORDS Lipid hydroperoxide; Calcium overload; Lactate dehydrogenase; Free radical scavenger; Guinea pig, ventricular muscle; Rat, ventricular myocytes


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 Cardiovasc ResHome page
P. Eaton, D. J Hearse, and M. J Shattock
Lipid hydroperoxide modification of proteins during myocardial ischaemia
Cardiovasc Res, August 1, 2001; 51(2): 294 - 303.
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