Pretreatment with topiroxostat and irbesartan improves cardiac function after myocardial infarction in rats

Background：Activation of angiotensin receptor type1 (AT1R) and xanthine oxidase (XO) generates reactive oxygen species (ROS), that causes cardiac dysfunction after myocardial infarction (MI). However, it remains unknown whether its inhibition could restore the cardiac function after MI. In the present study, we examined effects of irbesartan and topiroxostat on cardiac function after MI. Methods and results：We studied blood pressure and cardiac function in a rat myocardial infraction model using tail cuff system and echocardiography. Irbesartan and topiroxostat as well as vehicle were orally administered for 35 days to rats 7 days before MI induction. Neither irbesartan nor topiroxostat altered mean blood pressure and heart rate after MI. Treatment with either drugs significantly improved cardiac function after MI. The potency of topiroxostat to restore the cardiac function was approximately half of that of irbesartan. Conclusions：A non-purine XO inhibitor, topiroxostat improved cardiac function after MI, suggesting that like irbesartan, topiroxostat may be a promising drug to treat congestive heart failure after MI.