Cardioprotective Effects of Morphine and Inhibitors

The rats were randomized into eight groups (n = 20 per group). (1) Sham group: rats underwent thoracotomy, passing the ligature through the heart but without tying it (150 min). (2) I/R group: 30 min of ischemia and followed by 2 h of reperfusion. (3) IPostC group: 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h. (4) MP group: I/R followed by morphine administration (0.3 mg/kg [18 (link)] IV bolus; Sigma-Aldrich, St. Louis, MO, USA) 10 min before the beginning of reperfusion and then reperfused for 2 h. (5) MP + GA group: administration of the HSP90 inhibitor geldanamycin (GA, 1 mg/kg [19 (link)] IP; Sigma-Aldrich). (6) MP + GSK group: administration of the Akt inhibitor GSK-690693 (GSK, 20 mg/kg [20 (link)] IP; Med Chem Express, NJ, USA). (7) MP + PMX group: administration of the C5a inhibitor-PMX 205 (PMX, 1 mg/kg/day [21 (link)], administration for 28 days via drinking water; Med Chem Express, NJ, USA). (8) MP + QNZ group: administration of the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg [22 (link)]; IP, Selleck, USA). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion.