Rivaroxaban, a direct inhibitor of factor Xa, attenuates myocardial ischemia-reperfusion injury in rats at therapeutic concentrations - 26/03/18
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Résumé |
Introduction |
Acute myocardial infarction is a leading cause of death worldwide. Although highly beneficial, reperfusion of myocardium is associated with reperfusion injury. Indirect pharmacologic inhibition of factor Xa by fondaparinux has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury via the activation of the SAFE pathway. The link between the inhibition of factor Xa and the activation of this cardioprotective pathway remains unclear.
Objective |
To study the effect of a direct inhibitor of factor Xa, rivaroxaban (RIV), on myocardial I/R injury.
Method |
We investigated the ability of RIV to prevent I/R injury in a model of transient coronary ligation in rats. 40min of myocardial ischemia was followed by 120min of reperfusion. RIV (3mg/kg) was injected intraperitoneally (IP) 10min before reperfusion or given per os (PO) 1hour before reperfusion. Infarct size was assessed after 120min of reperfusion. RIV concentrations were measured after both administration protocols. Myocardial tissues were collected at 30min reperfusion for western-blots analysis.
Results |
RIV decreased infarct size by 19% when administrated IP (44.1% vs. 54.2% in RIV-treated rats and controls respectively, P<0.05) and by 21% when administrated PO (42.9% vs. 54.2% in RIV-treated rats and controls respectively, P<0.05). After IP administration, concentrations of RIV where higher than after PO administration (7244.3±1853ng/mL vs. 387.7±152.3ng/mL respectively). There was no effect of RIV on the phosphorylation of STAT-3, GSK-3β, AKT and ERK1/2.
Conclusion |
RIV decreased myocardial I/R injury in rats at concentrations similar to those known as antithrombotic in human therapeutics. Unlike FDX, this protective effect was not mediated through the activation of the cardioprotective pathways RISK and SAFE.
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Vol 10 - N° 2
P. 185-186 - avril 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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