BJA Advance Access originally published online on February 27, 2008
British Journal of Anaesthesia 2008 100(4):465-471; doi:10.1093/bja/aen022
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Hyperglycaemia blocks sevoflurane-induced postconditioning in the rat heart in vivo: cardioprotection can be restored by blocking the mitochondrial permeability transition pore
Laboratory of Experimental Intensive Care and Anaesthesiology, Academic Medical Center, Department of Anaesthesiology, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands
* Corresponding author. E-mail: n.c.hauck{at}amc.uva.nl
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.
Keywords: anaesthetics volatile, sevoflurane; cyclosporine A; heart, infarct; heart, postconditioning; hyperglycaemia
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