10.    Rosuvastatin promotes a cardioprotective metabolic environment in hearts subject
        to ischemia-reperfusion

Previously in our laboratory we investigated the cardioprotective actions of rosuvastatin (R) in hearts subjected to ischemia-reperfusion (I-RP). We could see that they were mediated, at least in part, by the activation of the Akt protein which promots the inhibition of GSK3B by inducing the attenuation of the Mitochondrial Permeability Transition Pore (MPTP) opening. In the present work we set out to investigate the metabolic environment involved in the aforementioned events and mitochondrial morphology in Langendorff perfused rat hearts subject to I-RP. Wistar female rats (250-300g body weight) fed ad libitum were used. R (3uM) and wortmannin (W 100nM), Akt inhibitor, were added 10 and 15 min before global I respectively. Hearts were subjected to 25 min of I and 60 min of RP. Tissue samples were taken at the end of stabilization and ischemia to determinate lactic acid and glycogen content, electronic microscopies were performed at the same time for assess mitochondrial damage. ANOVA (n=6/group). Lactic acid content were meaningfully lower in those hearts treated with R (μmoles/g dw): C (control): 146,28±6,60**; R: 56,68±6.77; W: 65,31±5,22; R+W: 61,35±4,10 (**p<0,01 against all groups), although paradoxically glycogen content was similar between hearts treated with R and group C (ug/100 mg dw): C: 148,76±32,86*; R: 120,73±25,49*; W: 288,39±21,77; R+W: 324,64±34,75 (*p<0,05 vs W y R+W). The glucose released by glycogenolysis could be participating in the cycle of the pentoses, therefore, we mean the activity of a key enzyme, glucose-6-phosphate dehydrogenase (G6PD), and the results showed an increase activity in those hearts treated with R at the end of ischemic period ( UI/g p: C: 1,76±0,14**; R: 3,08±0,17**; W: 1,39±0,19; R+W: 1,73±0,14) (**p<0,01 vs C, W y R+W) Electronic microscopy showed greater mitochondrial conservation in the group treated with R. Our results suggest that the metabolic environment fostered by the R would generate the necessary conditions to promote the attenuation of the MPTP and favor the better functioning of the heart subject to I-RP, accompanied by a greater preservation of the mitochondrial structure.