Journal of J. Trace Elements Med. BioI. Vol. 12, pp. 28-38 (1998) Trace Elements in Medicine and Biology © 1998 by Gustav Fischer Verlag Trace Elements and Cardioprotection: Increasing Endogenous Glutathione Peroxidase Activity by Oral Selenium Supplementation in Rats Limits Reperfusion-induced Arrhythmias S. TANGUY,F. BOUCHER, S. BESSE, V. DUCROS*, A. FAVIER* and J. DE LEIRIS Physiopathologie Cellulaire Cardiague, CNRS ESA 5077, Universite J. Fourier, Grenoble, France *Laboratoire de Biochimie C, Centre Hospitalier Regional de Grenoble, Grenoble, France (Received August/November 1997) Summary Oxyradicals have been implicated as a possible cause of reperfusion-arrhythmias (RA). However, the use of diverse exogenous oxyradical scavengers designed to reduce RA has given contradictory results. The aim of the present study was to determine whether enhancing the activity of the main endogenous enzyme involved in per- oxide elimination in cardiac cells, namely glutathione peroxidase, may limit RA in isolated heart preparations by increasing their antioxidant status.For this purpose, a group of 15 male Wi star rats received a selenium en- riched diet for ten weeks (l.5 mg Se/kg diet). Control animals (n=15) received a standard diet containing 0.05 mg Se/kg diet. The incidence or early ventricular arrhythmias was investigated during the reperfusion period following 10 min regional ischemia induced ex-vivo by left coronary artery ligation. Our results show that se- lenium-supplementation significantly increased the global selenium status of the animals. In the isolated heart preparations, the selenium supplementation induced a significant reduction of the severity of RA as assessed by the arrhythmia score and the limitation of the incidence of both ventricular tachycardia (control: 91 % vs sele- nium: 36 %, p<0.05) and irreversible ventricular fibrillation (control: 45 % vs selenium: 0 %, p<0.05). These effects were associated with a significant increase in cardiac mitochondrial and cytosolic glutathione peroxi- dase activities in both the left and the right ventricles. These results illustrate the potential protective effect of selenium against ischemia-reperfusion injury and suggest that peroxides might playa key role in the genesis of some aspects of the reperfusion syndrome. Keywords: Regional ischemia, reperfusion arrhythmias, oxygen free radicals, selenium, glutathione peroxi- dase, rat heart. Introduction Early reperfusion of ischemic cardiac tissue is gener- ally considered to be the only possible way to restore the Reprint requests to: Prof. Joel de Leiris, Groupe de Physio- pathologie CeIIulaire Cardiaque,CNRS ESA 5077, Universite Joseph Fourier, BP 53X38041 Grenoble Cedex, France ceJlular functions that have been altered by ischemia, and to prevent the evolution of ischemic myocardial cells to- wards necrosis. Nevertheless, reperfusion is often accom- panied by diverse manifestations of the so-called "reper- fusion syndrome" (1,2) including reversible mechanical dysfunction (myocardial stunning) and arrhythmias (3,4). The occurrence of reperfusion arrhythmias in the clinical