Abstract 13279: Effects of SBT-255 on Myocardial Infarct Size and No Reflow in a Rat Myocardial Ischemia/Reperfusion Model

Abstract

Background: We determined whether mitochondrial protective agents, elamipretide and SBT-255, could limit myocardial infarct (MI) size and the no reflow phenomenon in a standardized rat model. Methods and Results: Anesthetized rats were randomized into 3 groups (n = 15 in each group): (1) Saline control group; (2) Bolus dose of elamipretide (1 mg/kg body weight); (3) Bolus dose of SBT-255 (1 mg/kg body weight). The treatment was administered at 10 minutes after coronary artery occlusion. The coronary occlusion was maintained for 30 minutes followed by 3 hours of reperfusion. MI size (triphenyl tetrazolium chloride staining technique), expressed as a percentage of the ischemic risk zone (blue dye technique) was significantly lower in the SBT-255 treated group at 30.2 ± 5.0% versus 53.1 ± 4.0% in the saline group and 48.1 ± 5.1% in the elamipretide group (p=0.001). Area of no-reflow (thioflavin S technique) as a percentage of the risk zone was significantly smaller in the SBT-255 treated group (22.2 ± 5.4%) compared to the saline (38.0 ± 3.4%) and elamipretide groups (36.4 ± 5.0%; p=0.024). The Figure demonstrates the association between myocardial ischemic risk area and infarct size (panel A) as well as no-reflow size (panel B) among the 3 groups. The regression lines in both infarct size and no-reflow size shift downward in SBT-255 group compared to the saline and elamipretide group, indicating that, for the same size of risk area, the infarct size and no-reflow were smaller in the SBT-255 group than the other groups. Conclusions: SBT-255 treatment significantly reduced infarct size and no-reflow size compared to either saline or elamipretide treatment in an acute rat myocardial ischemia/reperfusion model.