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对抗冷缺血再灌注损伤的药理学策略。

Pharmacological strategies against cold ischemia reperfusion injury.

机构信息

Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, C/Rosselló 161, 7th floor, E-08036-Barcelona, Spain.

出版信息

Expert Opin Pharmacother. 2010 Mar;11(4):537-55. doi: 10.1517/14656560903547836.

Abstract

IMPORTANCE OF THE FIELD

Good organ preservation is a determinant of graft outcome after revascularization. The necessity of increasing the quality of organ preservation, as well as of extending cold storage time, has made it necessary to consider the use of pharmacological additives.

AREAS COVERED IN THIS REVIEW

The complex physiopathology of cold-ischemia-reperfusion (I/R) injury--and in particular cell death, mitochondrial injury and endoplasmic reticulum stress--are reviewed. Basic principles of the formulation of the different preservation solutions are discussed.

WHAT THE READER WILL GAIN

Current strategies and new trends in static organ preservation using additives such as trimetazidine, polyethylene glycols, melatonin, trophic factors and endothelin antagonists in solution are presented and discussed. The benefits and mechanisms responsible for enhancing organ protection against I/R injury are also discussed. Graft preservation was substantially improved when additives were added to the preservation solutions.

TAKE HOME MESSAGE

Enrichment of preservation solutions by additives is clinically useful only for short periods. For longer periods of cold ischemia, the use of such additives becomes insufficient because graft function deteriorates as a result of ischemia. In such conditions, the preservation strategy should be changed by the use of machine perfusion in normothermic conditions.

摘要

重要性的领域

良好的器官保存是移植后再血管化的结果的决定因素。提高器官保存质量的必要性,以及延长低温保存时间,使得有必要考虑使用药理添加剂。

在这篇综述中涉及

冷缺血再灌注(I / R)损伤的复杂病理生理学 - 特别是细胞死亡,线粒体损伤和内质网应激 - 进行了回顾。讨论了不同保存溶液配方的基本原则。

读者将获得什么

提出并讨论了在静态器官保存中使用添加剂(如曲美他嗪,聚乙二醇,褪黑素,营养因子和内皮素拮抗剂)的当前策略和新趋势。还讨论了增强器官对 I / R 损伤的保护作用的益处和机制。添加剂的加入极大地改善了供体器官的保存。

带回家的信息

添加剂对保存溶液的富集在临床上仅在短时间内有用。对于较长时间的冷缺血,由于缺血导致移植物功能恶化,这种添加剂的使用变得不足。在这种情况下,保存策略应通过在常温下使用机器灌注来改变。

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