Rivaroxaban, A Direct Inhibitor Of Factor Xa, Attenuates Myocardial Ischemia-Reperfusion Injury In Rats At Therapeutic Concentrations

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. 40 min of myocardial ischemia was followed by 120 min of reperfusion. RIV (3 mg/kg) was injected intraperitoneally (IP) 10 min before reperfusion or given per os (PO) 1 hour before reperfusion. Infarct size was assessed after 120 min of reperfusion. RIV concentrations were measured after both administration protocols. Myocardial tissues were collected at 30 min 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 P 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.