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  • Diabetes mellitus abrogates the cardioprotection of sufentanil against ischaemia/reperfusion injury by altering glycogen synthase kinase-3β.

Diabetes mellitus abrogates the cardioprotection of sufentanil against ischaemia/reperfusion injury by altering glycogen synthase kinase-3β.

Acta anaesthesiologica Scandinavica (2012-08-14)
Q L Chen, E W Gu, L Zhang, Y Y Cao, Y Zhu, W P Fang
ABSTRACT

Sufentanil is widely used in clinical anaesthesia because of its protective effects against ischaemia/reperfusion injury. Diabetes mellitus elevates the activity of glycogen synthase kinase-3β (GSK-3β), thereby increasing the permeability of mitochondrial transition pore. This study investigated the role of GSK-3β in ameliorating the cardioprotective effect of sufentanil post-conditioning in diabetic rats. Streptozotocin-induced diabetic rats and age-matched non-diabetic rats were subjected to 30 min of ischaemia and 120 min of reperfusion. Five minutes before reperfusion, rats were administered one of the following: a vehicle, sufentanil (1 μg/kg), or a GSK-3β inhibitor SB216763 (0.6 mg/kg). Myocardial infarct size, cardiac troponin I, and the activity of GSK-3β were then assessed. Sufentanil post-conditioning significantly reduced myocardial infarct size in the non-diabetic, but not in diabetic rats. SB216763 reduced infarct size in both diabetic and non-diabetic animals. Sufentanil-induced phospho-GSK-3β was reduced 5 min after reperfusion in diabetic rats, but not in non-diabetic rats. Sufentanil treatment was ineffective in preventing against ischaemia/reperfusion in diabetic rats, which is associated with the activation of GSK-3β. Our results also suggest that direct inhibition of GSK-3β may provide a strategy to protect diabetic hearts against ischaemia/reperfusion injury.

MATERIALS
Product Number
Brand
Product Description

Supelco
Sufentanil Citrate solution, 100 μg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Sufentanil-D5 solution, 100 μg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®