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Orotic acid and its salts chronically administered have been shown to significantly improve cardiac function in pathological settings associated with ischemia-reperfusion (I/R) injury. The aim of our study was to investigate the effect of magnesium orotate (Mg-Or) administration at the onset of post-ischemic reperfusion on myocardial function and infarct size (IS). Ex-vivo experiments performed on isolated perfused rat hearts were used to compare Mg-Or administration with a control group (buffer treated), ischemic post-conditioning, orotic acid treatment, and Mg[Cl.sub.2] treatment. Mg-Or administration was also investigated in an in-vivo model of regional I/R performed in rats undergoing reversible coronary ligation. The effect of Mg-Or on mitochondrial permeability transition pore (mPTP) opening after I/R was investigated in vitro to gain mechanistic insights. Both ex-vivo and in-vivo experiments showed a beneficial effect from Mg-Or administration at the onset of reperfusion on myocardial function and IS. In-vitro assays showed that Mg-Or significantly delayed mPTP opening after I/R. Our data suggest that Mg-Or administered at the very onset of reperfusion may preserve myocardial function and reduce IS. This beneficial effect may be related to a significant reduction of mPTP opening, a usual trigger of cardiac cell death following I/R. Key words: magnesium orotate, cardioprotection, ischemia-reperfusion, ischemic post-conditioning, in vivo. L'administration au long cours d'acide orotique ou de ses sels a montre un effet benefique sur la fonction cardiaque dans plusieurs situations pathologiques associees aux lesions d'ischemie-reperfusion (I/R). L'objectif de notre etude etait d'evaluer l'effet de l'orotate de magnesium (Mg-Or) administre en tout debut de reperfusion myocardique post ischemique sur la taille d'infarctus (TI) et la fonction cardiaque. Un modele ex vivo d'I/R sur cceur isole perfuse de rats a compare l'administration de Mg-Or avec les groupes experimentaux control (tampon), post conditionnement ischemique, acide orotique, et Mg[Cl.sub.2]. L'effet de Mg-Or a egalement ete evalue sur un modele in vivo d'I/R myocardique regional par ligature coronaire chez le rat. Une etude mecanistique a evalue l'effet de Mg-Or sur l'ouverture du port de permeabilite de transition mitochondriale (mPTP). L'administration de Mg-Or en debut de reperfusion sur les modeles ex vivo et in vivo entrame une diminution de la TI et une preservation de la fonction cardiaque. L'etude mecanistique montre que Mg-Or retarde l'ouverture du mPTP apres I/R myocardique. Nos resultats suggerent que Mg-Or administre en debut de reperfusion est susceptible de diminuer la TI et de preserver la fonction cardiaque. Cet effet est vraisemblablement lie a son action inhibitrice sur l'ouverture du mPTP, phenomene implique dans les processus de mort cellulaire post I/R myocardique. Mots-cles: orotate de magnesium, cardioprotection, ischemie-reperfusion, post conditionnement ischemique, in vivo., Introduction Myocardial infarction represents a major cause of morbidity and mortality worldwide. The cornerstone of treatment is represented by timely restoration of coronary reperfusion achieved either pharmacologically by thrombolysis and [...]