SR9009 treatment

The REV-ERB agonist SR9009 treatment was given in a blinded manner, intraperitoneally (i.p.) at a dose of 100 mg per kg in 15% cremophor, versus vehicle (15% cremophor), to mice after mI/R. The first treatment was given at ZT06 following reperfusion, then once daily for 5 days, and then all animals were maintained without any treatments for up to 8 weeks after mI/R. Dosage was based on murine studies of in vivo efficacy^13,14,45,50. In a separate study investigating only normal healthy hearts, mice were injected i.p. at ZT06 once per day for 2 weeks. A separate cohort of mice used to investigate the time-of-day effects of SR9009 treatment post-mI/R were given the drug at ZT18 at reperfusion and then for all 5 days, or ZT18 post-reperfusion followed by ZT06 once daily for 5 days. Another experiment investigated whether treatment was effective if given at ZT06 for 1, 3, or 5 days.