Weber N C, Schlack W
Department of Anaesthesiology, University of Amsterdam (AMC), Meibergdreef 9, NL-1100 DD, Amsterdam, The Netherlands.
Handb Exp Pharmacol. 2008(182):187-207. doi: 10.1007/978-3-540-74806-9_9.
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.
心脏具有强大的内源性心脏保护机制,该机制可由短时间缺血(如心绞痛发作时)触发,并在随后的缺血事件(如心肌梗死时)中保护心肌。这种重要的机制称为缺血预处理,已得到广泛研究,但通过诱导缺血进行干预的实际相关性主要局限于实验情况。最近的研究表明,许多挥发性麻醉剂可诱导类似的心脏保护机制,这在临床上比通过缺血诱导心脏保护更具相关性。在过去几十年中,多项实验室研究表明,接触吸入性麻醉剂会导致心肌蛋白质结构发生多种变化。通过对这些修饰(即激活)的靶酶进行功能阻断,证明蛋白质结构和分布的某些变化可通过麻醉预处理介导心脏保护作用。本章概述了我们目前对这一现象信号转导的理解。除了在缺血前进行干预(即预处理)外,还有另外两个时间窗,物质可能在此时与缺血再灌注过程相互作用,并可能改变损伤程度:(1)缺血期间或(2)缺血后(即再灌注期间)(后处理)。在动物实验中,挥发性麻醉剂也与这些机制相互作用(尤其是在缺血后立即),即通过后处理。由于心脏的缺血再灌注在多种临床情况下经常发生,如移植手术、冠状动脉搭桥术、瓣膜修复或血管手术期间,麻醉诱导的心脏保护可能是临床情况下保护心肌的一个有前景的选择。目前的初步研究证实了对替代结局参数的影响,如重症监护病房(ICU)住院时间或住院时间,或缺血后肌钙蛋白释放。在本章中,我们将总结目前对吸入性麻醉剂发挥的麻醉心脏保护三种机制的理解。