Jerome S N, Kong L, Korthuis R J
Department of PhyP6ology, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
J Invest Surg. 1994 Jan-Feb;7(1):3-16. doi: 10.3109/08941939409018278.
In recent years, considerable research efforts have been directed at elucidating the mechanisms underlying the pathophysiologic alterations associated with reperfusion (reoxygenation) of ischemic (hypoxic) skeletal muscle. This intensive effort has led to the accumulation of a large body of evidence supporting the concept that reactive oxygen metabolites, generated at the onset of reperfusion, initiate the formation and release of proinflammatory agents, which subsequently attract and activate granulocytes. The activated neutrophils adhere to the microvascular endothelium, extravasate, and release cytotoxic oxidants and hydrolytic enzymes. As a consequence of these pathologic events, vascular permeability and transcapillary fluid filtration are increased and the no-reflow phenomenon (ie, some capillaries fail to reperfuse upon reinstitution of blood flow) becomes apparent. These microvascular alterations may be of considerable functional importance since the marked accumulation of fluid in the interstitial spaces, coupled with the incomplete and maldistributed blood flow, increases the functional diffusion path length for nutrients. Thus cellular nutrition is limited during reperfusion, which in turn impairs the functional recovery of postischemic muscles. Moreover, the infiltrating neutrophils are able to direct a focussed attack on myocytes, thereby exacerbating contractile dysfunction and tissue injury during reperfusion. These observations indicate that alterations in the microcirculation play a critical role in the genesis of ischemia/reperfusion injury in skeletal muscle. This review summarizes the evidence we have accumulated in support of the view that reactive oxygen metabolites and neutrophils contribute to production of postischemic microvascular dysfunction and describes the experimental models we have used to examine the mechanisms involved in the pathogenesis of ischemia and reperfusion.
近年来，大量研究致力于阐明与缺血（缺氧）骨骼肌再灌注（复氧）相关的病理生理改变的潜在机制。这项深入的研究积累了大量证据，支持以下观点：再灌注开始时产生的活性氧代谢产物引发促炎介质的形成和释放，随后吸引并激活粒细胞。活化的中性粒细胞黏附于微血管内皮，渗出并释放细胞毒性氧化剂和水解酶。这些病理事件导致血管通透性增加和跨毛细血管液体滤过增加，无复流现象（即一些毛细血管在恢复血流后未能再灌注）变得明显。这些微血管改变可能具有相当重要的功能意义，因为间质空间中液体的明显积聚，加上血流不完全和分布不均，增加了营养物质的功能扩散路径长度。因此，再灌注期间细胞营养受到限制，进而损害缺血后肌肉的功能恢复。此外，浸润的中性粒细胞能够直接对肌细胞发动集中攻击，从而加剧再灌注期间的收缩功能障碍和组织损伤。这些观察结果表明，微循环的改变在骨骼肌缺血/再灌注损伤的发生中起关键作用。本综述总结了我们积累的证据，以支持活性氧代谢产物和中性粒细胞导致缺血后微血管功能障碍的观点，并描述了我们用于研究缺血和再灌注发病机制的实验模型。
