Mechanisms involved in the desflurane-induced post-conditioning of isolated human right atria from patients with type 2 diabetes

Background Desflurane triggers post-conditioning in the diabetic human myocardium. We determined whether protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK ATP ) channels, Akt, and glycogen synthase kinase-3β (GSK-3β) were involved in the in vitro desflurane-induced post-conditioning of human myocardium from patients with type 2 diabetes. Methods The isometric force of contraction (FoC) of human right atrial trabeculae obtained from patients with type 2 diabetes was recorded during 30 min of hypoxia followed by 60 min of reoxygenation. Desflurane (6%) was administered during the first 5 min of reoxygenation either alone or in the presence of calphostin C (PKC inhibitor) or 5-hydroxydecanoate (5-HD) (mitoK ATP channel antagonist). Phorbol 12-myristate 13-acetate (PKC activator) and diazoxide (a mitoK ATP channel opener) were superfused during early reoxygenation. The FoC at the end of the 60 min reoxygenation period was compared among treatment groups (FoC 60 ; mean and sd). The phosphorylation of Akt and GSK-3β was studied using western blotting. Results Desflurane enhanced the recovery of force [FoC 60 : 79 (3)% of baseline] after 60 min of reoxygenation when compared with the control group ( P >0.0001). Calphostin C and 5-HD abolished the beneficial effect of desflurane-induced post-conditioning (both P 60 when compared with the control group (both P P Conclusions Desflurane-induced post-conditioning in human myocardium from patients with type 2 diabetes was mediated by the activation of PKC, the opening of the mitoK ATP channels, and the phosphorylation of Akt and GSK-3β.