The factor Xa inhibitor rivaroxaban reduces cardiac dysfunction in a mouse model of myocardial infarction. Issue 167 (July 2018)

• Record Type: Journal Article
• Authors: Bode, Michael F.; Auriemma, Alyson C.; Grover, Steven P.; Hisada, Yohei; Rennie, Alex; Bode, Weeranun D.; Vora, Rashi; Subramaniam, Saravanan; Cooley, Brian; Andrade-Gordon, Patricia; Antoniak, Silvio; Mackman, Nigel
• Is Part Of: Thrombosis research. Issue 167(2018)
• Page Start: 128
• Page End: 134
• Publication Date: 2018-07
• Subjects: Cardiac remodeling -- Coagulation -- Factor Xa -- Myocardial infarction -- Protease-activated receptor -- Rivaroxaban; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2018.05.015
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: Rivaroxaban selectively inhibits factor Xa (FXa), which plays a central role in blood coagulation. In addition, FXa activates protease-activated receptor-2 (PAR-2). We have shown that PAR-2 −/− mice exhibit less cardiac dysfunction after cardiac injury. Material and methods: Wild-type (WT) and PAR-2 −/− mice were subjected to left anterior descending artery (LAD) ligation to induce cardiac injury and heart failure. Mice received either placebo or rivaroxaban chow either starting at the time of surgery or 3 days after surgery and continued up to 28 days. Cardiac function was measured by echocardiography pre-surgery and 3, 7 and 28 days after LAD ligation. We also measured anticoagulation, intravascular thrombi, infarct size, cardiac hypertrophy and inflammation at various times. Results: Rivaroxaban increased the prothrombin time and inhibited the formation of intravascular thrombi in mice subjected to LAD ligation. WT mice receiving rivaroxaban immediately after surgery had similar infarct sizes at day 1 as controls but exhibited significantly less impairment of cardiac function at day 3 and beyond compared to the placebo group. Rivaroxaban also inhibited the expansion of the infarct at day 28. Rivaroxaban did not significantly affect the expression of inflammatory mediators or a neutrophil marker at day 2 after LAD ligation. Delaying the start of rivaroxaban administration until 3 days after surgery failed to preserve cardiac function. In addition, rivaroxaban did not reduce cardiac dysfunction in PAR-2 −/− mice. Conclusions: Early administration of rivaroxaban preserves cardiac function in mice after LAD ligation. Graphical abstract: Highlights: Rivaroxaban reduces expansion of the infarct in mice after cardiac injury. Rivaroxaban reduces heart failure in mice after cardiac injury. Rivaroxaban does not affect inflammation in mice after cardiac injury. Rivaroxaban does not affect heart failure in PAR-2 −/− mice after cardiac injury.