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Figure 2 | Journal of Translational Medicine

Figure 2

From: Translation of TRO40303 from myocardial infarction models to demonstration of safety and tolerance in a randomized Phase I trial

Figure 2

Functional recovery and reduction of oxidative stress by TRO40303 in isolated rat hearts following ischemia-reperfusion. Isolated rat hearts were perfused using the Langendorff system by solutions of KH buffer containing 0.03% HPBCD with or without TRO40303 1 μM. A: left ventricular end diastolic pressure (LVEDP), B: coronary flow, C: developed pressure (Pdev), D: contractility (dP/dt) and E: rate pressure product (RPP) was evaluated in isolated rat hearts during 60 min of reperfusion following 30 min of no flow ischemia. A to E: Comparisons among groups were performed using a two-way ANOVA, ***: p < 0.001 vs 0.03% HPBCD. A significant improvement in functional recovery was observed for all the parameters when hearts were perfused with KH buffer containing TRO40303. Relative ascorbate levels were measured through ESR detection of dimethyl sulfoxide (DMSO)-stabilized ascorbyl free radical (AFR) in the effluents (F) at the 1st min of reperfusion and in the heart tissue (G) at the end of reperfusion. TRO40303 reduced the level of ascorbate release in the effluents while maintaining a higher level in heart tissue. DMPO-OH release was evaluated in the coronary effluents from hearts reperfused in the presence of 25 mM DMPO: typical spectra (H) recorded 3 min following onset of reflow for vehicle and TRO40303-treated samples; no signal was observed when hearts were perfused with 25 mM DMPO during normoxia; and determination of relative DMPO-OH levels (I) showing that TRO40303 1 μM reduced post-ischemic ROS release. Lipid peroxidation, evaluated by MDA-TBA in the heart ventricle at the end of reperfusion, was reduced in the hearts treated by TRO40303 compared to vehicle (J). F to J: Bars indicate mean ± S.E.M. and comparisons among groups were performed using a t-test *: p < 0.05, **: p < 0.01 vs 0.03% HPBCD (n = 6/group).

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