1. The mechanisms of cardio-protective effects of desflurane and sevoflurane at the time of reperfusion: anaesthetic post-conditioning potentially translatable to humans? 
S Lemoine, L Tritapepe, J.L. Hanouz, P.E. Puddu 
British Journal of Anaesthesia 
Volume 116, Issue 4, Pages (April 2016)
DOI: /bja/aev451
Copyright © 2016 The Author(s) Terms and Conditions

2. Fig 1
Schematic representation of the mechanisms by which the opening of mitoKATP and mPTP inhibition could induce cardio-protection in response to post-conditioning by desflurane and sevoflurane. The activation of G-protein coupled receptors including beta-adrenergic, adenosine and bradykinin, in response to the receptors’ stimulation by desflurane and sevoflurane PostC lead to the activation of a G protein (Gi or Gq), leading to activation of PKCε and the MAPKs. Activation of PKCε would induce mitoKATP opening. How the opening of mitoKATP channels is cardio-protective could be explained by the fact that it stimulates mitochondrial respiration and reduces calcium overload. During ischaemia-reperfusion, the opening of the mPTP pore at the time of reperfusion is because of in large part calcium entering the mitochondria via an uniport during ischaemia, calcium overload and intra-mitochondrial ATP depletion and oxidative stress. The opening of the mPTP, allowing the release of cytochrome C induces apoptosis (modified from Crisostomo and colleagues ). In response to the PostC by desflurane and sevoflurane : calcium overload in the mitochondrial matrix is decreased. At reperfusion, low calcium load, the level of ATP is preserved, and the production of oxygen free radicals is reduced which causes inhibition of mPTP opening, thus preventing the release of cytochrome C. Cyt C : cyochrome C; MAPK : Mitogen activated Protein kinase ; mito KATP : mitochondrial adenosine triphosphate-sensitive potassium channels; mPTP : mitochondrial permeability transition pore; NO : oxyde nitrique; PKC : protein kinase C; PostC : post-conditioning.
British Journal of Anaesthesia  , DOI: ( /bja/aev451)
Copyright © 2016 The Author(s) Terms and Conditions

3. Fig 2
Diagram depicting the effect of administration of desflurane and sevoflurane in early reoxygenation and the interaction between the myocardial post-conditioning induced by desflurane and sevoflurane and the RISK pathway. 1) Desflurane and sevoflurane PostC activate the Akt protein, ERK1/2, p70s6 K, NOS and inhibit the opening of mPTP. The pattern of activation most likely seems to be: in response to the administration of desflurane and sevoflurane, the PI3 K/Akt and MEK/ERK1/2 pathways are enabled. And Akt/PKB and ERK1/2 would trigger p70s6 K which could then inhibit GSK-3 beta; Akt also activate the NOS. 2) NO generated by NOS and GSK-3 beta inhibited would result in mPTP pore closure which results in cardio-protection. 3) Desflurane PostC via phosphorylation of Pim kinase protein and sevoflurane PostC via PI3 K/Akt and MEK/ERK1/2 pathways have anti-apoptotic effects. ERK : extra cellular signal regulated kinase; GSK-3 beta : glycogen synthase kinase-3 beta; MEK; mitogen activated protein kinase kinase; mPTP : mitochondrial permeability transition pore; NO : nitric oxyde; NOS: nitric oxide synthase; p70S6K : p70S6 kinase; PI3K : phosphatidylinositol 3-Kinase; PostC : post-conditioning; RISK : Reperfusion Injury Salvage Kinase.
British Journal of Anaesthesia  , DOI: ( /bja/aev451)
Copyright © 2016 The Author(s) Terms and Conditions

4. Fig 3
The anti-apoptotic effects of desflurane and sevoflurane induced post-conditioning. 1) Desflurane and sevoflurane PostC decrease the Bax expression and enhanced the Bcl-2 expression, moreover, caspase 3 and 9 were inactivated and BAD phosphorylated by sevoflurane PostC, the global effect is an anti-apoptotic effect. 2) Although few ROS generation are necessary for triggering desflurane PostC, it seems that sevoflurane PostC decreases the excessive ROS generation (‘burst of ROS’) in early reperfusion, preventing myocardial ischaemia-reperfusion injury. mPTP : mitochondrial permeability transition pore; PostC : post-conditioning; ROS : reactive oxygen species.
British Journal of Anaesthesia  , DOI: ( /bja/aev451)
Copyright © 2016 The Author(s) Terms and Conditions