Enhanced glucose uptake via GLUT4 fuels recovery from calcium overload after ischaemia–reperfusion injury in sevoflurane- but not propofol-treated hearts

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Enhanced glucose uptake via GLUT4 fuels recovery from calcium overload after ischaemia–reperfusion injury in sevoflurane- but not propofol-treated hearts E. Lucchinetti, L. Wang, K.W.S. Ko, H. Troxler, M. Hersberger, L. Zhang, M.A. Omar, G.D. Lopaschuk, A.S. Clanachan, M. Zaugg British Journal of Anaesthesia Volume 106, Issue 6, Pages 792-800 (June 2011) DOI: 10.1093/bja/aer065 Copyright © 2011 The Author(s) Terms and Conditions

Fig 1 Changes in LVW (ΔLVW, a) and myocardial efficiency (ΔME, b). IR, hearts exposed to ischaemia–reperfusion; SEVO+IR, hearts exposed to ischaemia–reperfusion and treated with 2 vol% sevoflurane before and after ischaemia; PROP100+IR, hearts exposed to ischaemia–reperfusion and treated with 100 µM propofol before and after ischaemia; INTRA100+IR, the corresponding Intralipid control group. Complete haemodynamic data were obtained for six hearts in each group except for IR and INTRA100+IR with only five hearts (also see Supplementary Table S1). Complete metabolic data were obtained in six hearts of each group except for IR and SEVO+IR with five hearts and INTRA+IR with four hearts. P-values were computed using non-parametric tests. British Journal of Anaesthesia 2011 106, 792-800DOI: (10.1093/bja/aer065) Copyright © 2011 The Author(s) Terms and Conditions

Fig 2 Intracellular Ca2+ concentrations at the end of ischaemia (a) and at the end of reperfusion (diastolic, b; systolic, c; and transient amplitude, d) in untreated hearts (IR, n=5) or in hearts that were exposed to sevoflurane (2 vol%, SEVO+IR, n=6), propofol (100 µM, PROP100+IR, n=6), or Intralipid (INTRA100+IR, n=5). P-values were computed using non-parametric tests. British Journal of Anaesthesia 2011 106, 792-800DOI: (10.1093/bja/aer065) Copyright © 2011 The Author(s) Terms and Conditions

Fig 3 Changes in rates of GOX (ΔGOX, a), FOX (ΔFOX, b), and acetyl-CoA production (c) during reperfusion in untreated hearts (IR, n=5) or in hearts that were exposed to sevoflurane (2 vol%, SEVO+IR, n=5), propofol (100 µM, PROP100+IR, n=6), or Intralipid (INTRA100+IR, n=4). P-values were computed using non-parametric tests. British Journal of Anaesthesia 2011 106, 792-800DOI: (10.1093/bja/aer065) Copyright © 2011 The Author(s) Terms and Conditions

Fig 4 Regression plots with 95% confidence intervals for correlations between changes in GOX rates and peak Ca2+ concentrations during ischaemia (a: R=0.851; standard error of estimate=0.087), changes in diastolic (b: R=0.847; standard error of estimate=0.088), and systolic (c: R=0.800; standard error of estimate=0.099) Ca2+ concentrations for untreated hearts (IR) or for hearts exposed to sevoflurane (2 vol%, SEVO+IR). British Journal of Anaesthesia 2011 106, 792-800DOI: (10.1093/bja/aer065) Copyright © 2011 The Author(s) Terms and Conditions

Fig 5 GLUT4 expression, AMPK, and PDH activities in untreated hearts (IR) or in hearts exposed to sevoflurane (2 vol%, IR+SEVO). (a) Representative western blots (n=5 per group) of GLUT4 expression in lipid rafts and quantification to flotillin. (b) Representative western blots of AMPK and activity estimated from the ratio of pAMPK and total AMPK. α-Actin was used as a loading control (n=4 for each group). (c) PDH activity calculated as active over total PDH (n=5 for each group). P-values were computed using Student's t-test or the Wilcoxon–Mann–Whitney test (WMW). British Journal of Anaesthesia 2011 106, 792-800DOI: (10.1093/bja/aer065) Copyright © 2011 The Author(s) Terms and Conditions