Lehr H A, Menger M D, Messmer K
Institute for Surgical Research, University of Munich, Germany.
J Lab Clin Med. 1993 Apr;121(4):539-45.
Leukocyte activation, adhesion, and emigration serve a protective role during a well-contained inflammatory response. However, under certain pathologic conditions such as endotoxemia, inflammatory bowel disease, and ischemia-reperfusion injury, leukocytes may turn against the host and aggravate--rather than prevent--tissue damage. Numerous experimental studies have been performed during the last decade to investigate the pathophysiologic role of leukocyte accumulation and adhesion during ischemia/reperfusion injury of various organs, in particular of the myocardium. Most of the latter studies investigated whether the consequences of experimental myocardial infarction could be attenuated by interventions aimed at the inhibition of chemotactic leukocyte infiltration or adhesion (or both) to microvascular endothelial cells. Although many promising results were reported, the consequent step towards an introduction of these strategies into experimental or even routine clinical management of patients with myocardial infarction has so far not been undertaken. In this manuscript, the authors try to give an overview on the state of the art of "antileukocyte" strategies in myocardial ischemia-reperfusion injury and to offer explanations for incongruent data obtained with diverse experimental approaches (animal species, treatment modalities, surgical and anesthesiologic artifacts, techniques for morphologic and functional evaluation of tissue damage). The authors conclude that long-term preclinical studies on suitable animal models, thoroughly investigating the positive and negative effects of antileukocyte interventions on the functional consequences of myocardial ischemia-reperfusion injury, are mandatory before the first clinical trial can be advocated.
在炎症反应得到良好控制的过程中，白细胞的激活、黏附和移出发挥着保护作用。然而，在某些病理状态下，如内毒素血症、炎症性肠病和缺血-再灌注损伤，白细胞可能会转而攻击宿主，加重而非预防组织损伤。在过去十年中，已经进行了大量实验研究，以探讨白细胞积聚和黏附在各种器官，尤其是心肌缺血/再灌注损伤过程中的病理生理作用。大多数后续研究调查了针对抑制趋化性白细胞浸润或白细胞与微血管内皮细胞黏附（或两者皆抑制）的干预措施是否能减轻实验性心肌梗死的后果。尽管报告了许多有前景的结果，但迄今为止尚未迈出将这些策略引入心肌梗死患者的实验甚至常规临床管理的后续步骤。在本手稿中，作者试图概述心肌缺血-再灌注损伤中“抗白细胞”策略的现状，并为不同实验方法（动物物种、治疗方式、手术和麻醉假象、组织损伤形态学和功能评估技术）获得的不一致数据提供解释。作者得出结论，在倡导首次临床试验之前，必须对合适的动物模型进行长期临床前研究，全面调查抗白细胞干预对心肌缺血-再灌注损伤功能后果的正负影响。
