Inhalational anaesthetics and cardioprotection.
The heart has a strong endogenous cardioprotection mechanism that can be triggered by short periods of ischaemia (like during angina) and protects the myocardium during a subsequent ischaemic event (like during a myocardial infarction). This important mechanism, called ischaemic pre-conditioning, has been extensively investigated, but the practical relevance of an intervention by inducing ischaemia is mainly limited to experimental situations. Research that is more recent has shown that many volatile anaesthetics can induce a similar cardioprotection mechanism, which would be clinically more relevant than inducing cardioprotection by ischaemia. In the last few decades, several laboratory investigations have shown that exposure to inhalational anaesthetics leads to a variety of changes in the protein structure of the myocardium. By a functional blockade of these modified (i.e. activated) target enzymes, it was demonstrated that some of these changes in protein structure and distribution can mediate cardioprotection by anaesthetic pre-conditioning. This chapter gives an overview of our current understanding of the signal transduction of this phenomenon. In addition to an intervention before ischaemia (i.e. pre-conditioning), there are two more time windows when a substance may interact with the ischaemia-reperfusion process and might modify the extent of injury: (1) during ischaemia or (2) after ischaemia (i.e. during reperfusion) (postconditioning). In animal experiments, the volatile anaesthetics also interact with these mechanisms (especially immediately after ischaemia), i.e. by post-conditioning. Since ischaemia-reperfusion of the heart routinely occurs in a variety of clinical situations such as during transplant surgery, coronary artery bypass grafting, valve repair or vascular surgery, anaesthetic-induced cardioprotection might be a promising option to protect the myocardium in clinical situations. Initial studies now confirm an effect on surrogate outcome parameters such as length of ICU or in-hospital stay or post-ischaemic troponin release. In this chapter, we will summarize our current understanding of the three mechanisms of anaesthetic cardioprotection exerted by inhalational anaesthetics.
Weber
N C
NC
Department of Anaesthesiology, University of Amsterdam (AMC), Meibergdreef 9, NL-1100 DD, Amsterdam, The Netherlands. N.C.hauck@amc.uva.nl
Schlack
W
W
D018685:Anesthetics, Inhalation / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D006321:Heart / Q000187:drug effects*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D018685:Anesthetics, Inhalation