Comparison of the effects of erythropoietin, Akt activator, on the direct cardioprotective effects of rosuvastatin in hearts subject to ischemia (IS)-reperfusión (RP) in the Langendorff model.

MESTRE CORDERO, VICTORIA; HERMANN, ROMINA; VELEZ, DEBORA; MOURGLIA, JULIETA; PEREGO, JULIANA; MARINA PRENDES, MARIA GABRIELA

Mar del Plata

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

Sociedad Argentina de Investiación Clínica

In previous work carried out in our laboratory we could show thatAkt was involved, at least in part, in the direct cardioprotective effectsof rosuvastatin (R,3uM). The aim of the present work was toinvestigate whether the Erythropoietin (E,2mU/ml), an Akt activator,promoted the same response as that exerted by R in the presenceor absence of wortmannin (W,100nM), a PI3K/Akt inhibitor.Hearts from Wistar rats (200-250g) were subjected to 25 min of ISand 60 min of RP. E and W were added 10 and 15 min before globalIS respectively. The contractility was evaluated by left ventriculardeveloped pressure (LVDP), rate-pressure product (RPP), peak rateof contraction and peak rate of relaxation (±dP/dt) and left ventricularend-diastolic pressure (LVEDP). Tissue samples were taken toassess mitochondrial damage by electron microscopies and to evaluateinfarct size. Mitochondria were isolated to evaluate the openingof mitochondrial permeability transition pore (MPTP) against differentcalcium concentrations. Infarct size was also measured by triphenyltetrazolium. ANOVA, (n=6/group).E improved the postischemic recovery of contractility in the sameway as R, although LVDP presented a greater increase than developedby R (5 min RP, RPP(%): C:7±2, W:10±3, R:24±6*, R+W:9±3,E:24±3*, E+W:11±3, *p<0,05 vs C,W, R+W,E+W; LVEDP (%):C:15±2,W:12±2,R: 3±0,2**, R+W:10±2, E:12±2@, E+W:21±3, @p<0,05 vs C,W,R+W,E+W, **p<0,01 vs C,W, R+W,E,E+W). R andE delayed the opening of the MPTP to 300uM CaCl2, while the useof w caused the opening of the MPTP to 200uM CaCl2. Electronmicroscopy showed greater mitochondrial conservation in bothgroups, R and E. The analysis of infarct size in hearts treated with Edid not show significant differences with R.Our results suggest that the cardioprotection exerted by rosuvastatincould be partly mediated by Akt, although it remains to investigatethe possible regulation exerted by E on GSK3β.