Figure 1

Dose effect and therapeutic window of TRO40303 in a myocardial infarction model in rats. Infarct sizes (IS) were quantified after 24 h coronary artery reperfusion (CAR) following 35 min of coronary artery occlusion (CAO), and calculated for each group as percentage of the area at risk (AAR) and then expressed as a percentage of the IS of the control group for each dose. N is the number of treated rats per group; circles are individual values while the mean ± S.E.M is indicated by black bars for each group; **: p < 0.01 and ***: p < 0.001 versus control. A) TRO40303 formulated in IL30 was administrated by i.v. bolus to rats 10 min before CAR. The doses of 1, 3 and 10 mg/kg provided significant protection in this ischemia-reperfusion model while 0.3 mg/kg did not have a significant effect using ANOVA followed by Dunnett’s post test. The average IS of the control group (vehicle 100%) corresponded to 43.62 ± 0.04% of the AAR. B) Plasma level of TRO40303 expressed in μg/mL during 24 h after i.v. bolus to satellite rats corresponding to the four doses tested in the IL30 formulation and compared to a pharmacokinetic profile of the 2.5 mg/kg dose in HPBCD previously shown as active. C) One mg/kg TRO40303 formulated in IL30 reduced infarct size significantly when administrated by i.v. bolus to rats 10 min before CAO, but not 10 min after CAR as evaluated by Student T-Test. D) Heart level of TRO40303 at 5 min after reperfusion in ischemic (AAR) or remainder of left ventricle (LV) after administration of 1 mg/kg TRO40303 formulated in IL30.