A. Time course of LVDP changes by E2 +/- drugs during the I/R protocol (scheme at top). E2-induced protection during reperfusion was diminished by cotreatment during the whole protocol with MEK1/2 inhibitor, U0126 and with PKC translocation inhibitor, chelerythrine chloride (CC) but not with PI-3K inhibitor, LY294002. B. Heart sections of same heart in each condition stained at the end of the reperfusion period. White areas are infarcted zones. LY294002 co-treatment failed to inhibit E2-mediated prevention of heart infarct. C,D,E. Mean values of Rate Pressure Product (RPP), and % infarct size in control hearts (ctrl, perfused with vehicle) and hearts treated with E2 (40 nM), E2 (40 nM)+U0126 (1 μM), E2 (40 nM)+LY294002 (10 μM), and E2 (40 nM)+CC (1 μM). RPP and dP/dt max were obtained by averaging the last 2 min of reperfusion. Values are expressed as mean±SEM; *, P<0.05 E2-treated group versus control (n = 6-8/group); #, P<0.05 E2+U0126 versus E2-treated group; +, P<0.05 E2+CC versus E2-treated group (n = 4-7/group). Functional values as a function of time are given in Table 2. All values were obtained using WT male mice.