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      Peri-operative anaesthetic myocardial preconditioning and protection – cellular mechanisms and clinical relevance in cardiac anaesthesia

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      1 , 2
      Anaesthesia
      BlackWell Publishing Ltd

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          Abstract

          Preconditioning has been shown to reduce myocardial damage caused by ischaemia–reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting.

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          Most cited references115

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          Desflurane and Sevoflurane in Cardiac Surgery: A Meta-Analysis of Randomized Clinical Trials

          The authors performed a meta-analysis to investigate whether the cardioprotective effects of volatile anesthetics translate into decreased morbidity and mortality in patients undergoing cardiac surgery. It is commonly believed that the choice of the primary anesthetic agent does not result in different outcomes after cardiac surgery. Recent evidence, however, has indicated that volatile anesthetics improve postischemic recovery at a cellular level, in isolated hearts, in animals, and in humans. Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment and comparison of a total intravenous anesthesia regimen versus an anesthesia plan including desflurane or sevoflurane performed on cardiosurgical patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The endpoints were the rate of perioperative myocardial infarction and hospital mortality. The search yielded 22 studies, involving 1,922 patients. Volatile anesthetics were associated with significant reductions of myocardial infarctions (24/979 [2.4%] in the volatile anesthetics group v 45/874 [5.1%] in the control arm, odds ratio [OR] = 0.51 [0.32-0.84], p for effect = 0.008, and p for heterogeneity = 0.77) and mortality (4/977 [0.4%] v 14/872 [1.6%], OR = 0.31 [0.12-0.80], p for effect = 0.02, and p for heterogeneity = 0.88). Desflurane and sevoflurane have cardioprotective effects that result in decreased morbidity and mortality. The present data show for the first time that the choice of an anesthetic regimen based on administration of halogenated anesthetics is associated with a better outcome after cardiac surgery.
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            Sevoflurane preserves the endothelial glycocalyx against ischaemia-reperfusion injury.

            Healthy vascular endothelium is coated by the glycocalyx, important in multiple endothelial functions, but destroyed by ischaemia-reperfusion. The impact of volatile anaesthetics on this fragile structure has not been investigated. We evaluated the effect of cardiac pre- and post-conditioning with sevoflurane on integrity of the endothelial glycocalyx in conjunction with coronary vascular function. Isolated guinea pig hearts perfused with Krebs-Henseleit buffer underwent 20 min stopped-flow ischaemia (37 degrees C), either without or with 1 MAC sevoflurane. This was applied for 15 min before, for 20 min after, or both before and after ischaemia. Transudate was collected for assessing coronary net fluid extravasation and histamine release by mast cells. Coronary release of syndecan-1 and heparan sulphate was measured. In additional experiments with and without continuous sevoflurane, cathepsin B and tryptase beta-like protease activity were measured in effluent. Hearts were perfusion-fixed to visualize the endothelial glycocalyx. Ischaemia led to a significant (P<0.05) increase by 70% in transudate formation during reperfusion only in hearts without sevoflurane. This was accompanied by significant (P<0.05) increases in heparan sulphate (four-fold) and syndecan release (6.5-fold), with electron microscopy revealing massive degradation of glycocalyx. After ischaemia, histamine was released into transudate, and cathepsin B activity increased in effluent (P<0.05). Sevoflurane application attenuated all these changes, except for histamine release. Sevoflurane protects the endothelial glycocalyx from ischaemia-reperfusion-induced degradation, with both preconditioning and rapid post-conditioning being successful. The mechanism seems to involve attenuation of lysosomal cathepsin B release and to be independent from tissue mast cell degranulation.
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              Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery.

              Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival.
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                Author and article information

                Journal
                Anaesthesia
                Anaesthesia
                anae
                Anaesthesia
                BlackWell Publishing Ltd (Oxford, UK )
                0003-2409
                1365-2044
                April 2015
                12 March 2015
                : 70
                : 4
                : 467-482
                Affiliations
                [1 ]Department of Anaesthetics, King's College Hospital NHS Foundation Trust London, UK
                [2 ]Department of Anaesthesia and Intensive Care, Papworth Hospital Cambridge, UK
                Author notes
                Correspondence to: G. Kunst Email: gudrun.kunst@ 123456kcl.ac.uk

                This paper is accompanied by an editorial: Anaesthesia 2015; 70: 379–83.

                Article
                10.1111/anae.12975
                4402000
                25764404
                8319b094-74b7-41cc-9f93-b0ec3ac66173
                © 2015 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists of Great Britain and Ireland

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 05 November 2014
                Categories
                Review Articles

                Anesthesiology & Pain management
                Anesthesiology & Pain management

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