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Aim: The cardioprotective effects afforded by volatile anesthetics, i.e. isoflurane, during heart surgery may be due to preconditioning of the myocardium through the activation of KATP channels. The aims of this study were to establish whether glibenclamide prevents the isoflurane-induced cardioprotection in diabetic patients undergoing coronary surgery (CABG) and whether this cardioprotective effect can be restored by preoperative shift from glibenclamide to insulin therapy., Methods: We enrolled 60 patients undergoing CABG. Twenty consecutive non-diabetic patients were randomized to receive conventional anesthesia (CA) or conventional anesthesia plus isoflurane (ISO) (added to the inspired oxygen before starting cardiopulmonary bypass); 40 consecutive diabetic patients in chronic treatment with oral glibenclamide were randomized to conventional anesthesia (G-CA), conventional anesthesia plus isoflurane (G-ISO), conventional anesthesia after shifting to insulin (I-CA) or conventional anesthesia plus isoflurane after shifting to insulin (I-ISO). Serum levels of cardiac troponin I (CTnI) and CK-MB, as markers of ischemic injury, were obtained 1, 24, 48 and 96 hours, postoperatively., Results: Postoperative peak levels of CTnI and CK-MB were lower in ISO than in CA (0.5+/-0.3 vs 2.8+/-2.2 ng/ml, p<0.05 and 61+/-27 vs 79+/-28 U/L, p<0.05, respectively), as well as in I-CA and I-ISO than G-CA and G-ISO groups (0.5+/-0.7 and 0.7+/-0.9 vs 3.5+/-3 and 2.7+/-2.5 ng/ml, p<0.05; 47+/-7 and 41+/-5 vs 85+/-28 and 50+/-23 U/L, p<0.05, respectively). No significant differences were detected in postoperative hemodynamic variables or in-hospital outcome., Conclusion: This prospective randomized study shows a cardioprotective effect of preoperative administration of isoflurane during CABG. Such an effect is prevented by glibenclamide, but can be restored in diabetic patients by preoperative shift from glibenclamide to insulin.