RIVAROXABAN IMPROVES MYOCARDIAL ISCHEMIA REPERFUSION INJURY COMPLICATIONS IN OBESE RATS

摘要

Rivaroxaban is a direct inhibitor for Factor Xa that used orally for prevention and treatment of thromboembolic disorders through inhibition of thrombin synthesis. In this study we hypothesis that rivaroxaban pretreatment might play a role in reducing the complications of myocardial ischemic reperfusion injury (IRI) in a rat model of obesity. R- hirudin (a commercially available anticoagulant drug used previously in attenuating the harmful effects of myocardial IRI) was used as a positive control in this study. To achieve this hypothesis, male Wistar albino rats were randomly assigned into 4 groups (n = 6 per group): control subjected to IRI, obese subjected to IRI, obese rats pretreated with r- hirudin (1.8 mg/kg body weight) then subjected to IRI, obese pretreated with Rivaroxaban (3 mg/kg body weight/day) then subjected to IRI. Obesity was induced by feeding rats high fat diet. Myocardial ischemia was induced by left anterior descending artery ligation (LAD). The obese rats subjected to IRI showed significant increases in the inflammatory markers (myocardial angiotensin II, tumor necrosis factor alpha (TNF- α), interleukin 8 (IL-8) contents and monocyte chemoattractant protein 1 (MCP-1) gene expression) compared with control rats subjected to IRI. A significant increase in serum creatine kinase MB (CK-MB) activity was also observed in obese rats subjected to IRI compared to control rats subjected to IRI. Rivaroxaban pretreatment to obese rats that subjected to IRI showed a significant decrease in the inflammatory markers likely through inhibition of thrombin synthesis; a mediator of myocardial ischemia reperfusion injury. Histological examination and measuring the percentage of infraction of cardiac tissue showed a significant improvement in the rivaroxaban pretreated rats compared to obese rats subjected to IRI.