Siracusano Luca, Girasole Viviana, Alvaro Simona, Chiavarino Nunziata Di Marco
Department of Neuroscience, Psychiatric and Anaesthesiological Sciences, University of Messina, School of Medicine, Policlinico Universitario G. Martino, Italy.
J Cardiovasc Med (Hagerstown). 2006 Feb;7(2):86-95. doi: 10.2459/01.JCM.0000199792.32479.ce.
The biological bases and the clinical applications of ischaemic and anaesthetic preconditioning are reviewed. Ischaemic preconditioning is an endogenous defensive phenomenon of the myocardium in which brief periods of ischaemia followed by reperfusion reduce the infarct size induced by longer ischaemic stimuli; both an early and a late phase may be distinguished. In the early phase, the mediators released activate ATP-dependent potassium channels and kinase cascade; these enzymes migrating at the level of various subcellular structures phosphorylate some end-effectors responsible for cardioprotection. Several molecules that are involved in the regulation of cell death during ischaemia-reperfusion injury have been proposed for such a role, including mitochondrial ATP-dependent potassium channels, connexins and cytoskeletal and mitochondrial proteins. In the late phase, the triggers and mediators themselves, plus nitric oxide, are responsible for the genetic reprogramming providing a protective effect via ex-novo synthesis of proteins. Volatile halogenated anaesthetics may induce a particular sort of pharmacological preconditioning, anaesthetic preconditioning, which presents some differences in the biochemical signalling mechanism but is able to give protection comparable to the ischaemic form. Anaesthetic preconditioning presents obvious advantages compared to ischaemic preconditioning, and researchers have tried to take advantage of this in the clinical setting, in cardiac surgical patients, in neuroprotection and to prolong the survival of organs destined for transplantation.
本文综述了缺血预处理和麻醉预处理的生物学基础及其临床应用。缺血预处理是心肌的一种内源性防御现象，即短暂的缺血后再灌注可减小较长时间缺血刺激所诱导的梗死面积；可分为早期和晚期两个阶段。在早期阶段，释放的介质激活ATP依赖性钾通道和激酶级联反应；这些在各种亚细胞结构水平迁移的酶使一些负责心脏保护的终效应器磷酸化。缺血再灌注损伤期间参与细胞死亡调节的几种分子被认为具有这样的作用，包括线粒体ATP依赖性钾通道、连接蛋白以及细胞骨架和线粒体蛋白。在晚期阶段，触发因素和介质本身，加上一氧化氮，通过蛋白质的重新合成负责基因重编程，从而提供保护作用。挥发性卤化麻醉剂可诱导一种特殊的药理学预处理，即麻醉预处理，其在生化信号传导机制上存在一些差异，但能够提供与缺血预处理相当的保护作用。与缺血预处理相比，麻醉预处理具有明显优势，研究人员试图在临床环境中利用这一点，应用于心脏手术患者、神经保护以及延长供移植器官的存活时间。
