Hyperglycaemia blocks sevoflurane-induced postconditioning in the rat heart in vivo: cardioprotection can be restored by blocking the mitochondrial permeability transition pore

Background. Recent studies showed that hyperglycaemia (HG) blocks anaesthetic-induced preconditioning. The influence of HG on anaesthetic-induced postconditioning ( post) has not yet been determined. We investigated whether sevoflurane (Sevo)-induced postconditioning is blocked by HG and whether the blockade could be reversed by inhibiting the mitochondrial permeability transition pore (mPTP) with cyclosporine A (CsA). Methods. Chloralose-anaesthetized rats (n = 7-11 per group) were subjected to 25 min coronary artery occlusion followed by 120 min reperfusion. Postconditioning was achieved by administration of 1 or 2 MAC sevoflurane for the first 5 min of early reperfusion. HG was induced by infusion of glucose 50% (G 50) for 35 min, starting 5 min before ischaemia up to 5 min of reperfusion. CsA (5 or 10 mg kg(-1)) was administered i.v. 5 min before the onset of reperfusion. At the end of the experiments, hearts were excised for infarct size measurements. Results. Infarct size (% of area at risk) was reduced from 51.4 (5.0)% [mean(SD)] in controls to 32.7 (12.8)% after sevoflurane postconditioning (Sevo-post) ( P, <0.05). This infarct size reduction was completely abolished by HG [51.1 (13.2)%, P, 0.05 vs Sevo-post], but was restored by administration of sevoflurane with CsA [35.2 (5.2)%, P, 0.05 vs HG+Sevo-post]. Increased concentrations of sevoflurane or CsA alone could not restore cardioprotection in a state of HG [Sevo-post2, 54.1 (12.6)%, P. 0.05 vs HG+Sevo- post; CsA10, 58.8 (11.3)%, P > 0.05 vs HG+CsA]. Conclusions. Sevoflurane-induced postconditioning is blocked by HG. Inhibition of the mPTP with CsA is able to reverse this loss of cardioprotection