• R Huhn, A Heinen, N C Weber, M W Hollmann, W Schlack, and B Preckel.
• Laboratory of Experimental Intensive Care and Anaesthesiology, Academic Medical Center, Department of Anaesthesiology, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands.
• Br J Anaesth. 2008 Apr 1; 100 (4): 465-71.

BackgroundRecent 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).MethodsChloralose-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.ResultsInfarct 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].ConclusionsSevoflurane-induced postconditioning is blocked by HG. Inhibition of the mPTP with CsA is able to reverse this loss of cardioprotection.

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