Reperfusion therapy-What's with the obstructed, leaky and broken capillaries?
Reperfusion therapy-What's with the obstructed, leaky and broken capillaries?
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DOI：
10.1016/j.pathophys.2017.09.003
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发表时间：
2017-12-01
期刊：
影响因子：
--
通讯作者：
Kvietys, Peter R
中科院分区：
文献类型：
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作者：
Granger, D Neil;Kvietys, Peter R
微血管功能障碍被公认为是组织对缺血和再灌注（I/R）的损伤反应中的早期和速率决定因素。严重的内皮细胞功能障碍，可以在没有明显形态学细胞损伤的情况下发展，是伴随I/R的微血管异常的主要潜在原因。虽然I/R诱导的微血管功能障碍以不同的方式表现，但在实验和临床环境中受到广泛关注的两种反应是毛细血管灌注受损（无复流）和内皮屏障失效并转变为出血。这些反应正在成为组织损伤反应严重程度的潜在重要决定因素，越来越多的临床证据表明，它们可预测再灌注治疗后的临床结局。这篇综述提供了一个总结的动物研究，集中在可能的基础上发生的无复流和出血缺血组织再灌注后的机制，并解决了临床证据，牵连这些血管事件的缺血性脑（中风）和心脏（心肌梗死）再灌注治疗的反应。由于活性氧（ROS）和基质金属蛋白酶（MMP）经常被调用作为触发器的微血管功能障碍引起的I/R，这些介质的潜在作用和来源进行了讨论。文献中的现有证据证明，对再灌注治疗后心脏和大脑中无复流和出血的发展越来越感兴趣，并表明这些血管事件可能预示不良临床结局，并需要制定有针对性的治疗策略。
Microvascular dysfunction is well established as an early and rate-determining factor in the injury response of tissues to ischemia and reperfusion (I/R). Severe endothelial cell dysfunction, which can develop without obvious morphological cell injury, is a major underlying cause of the microvascular abnormalities that accompany I/R. While I/R-induced microvascular dysfunction is manifested in different ways, two responses that have received much attention in both the experimental and clinical setting are impaired capillary perfusion (no-reflow) and endothelial barrier failure with a transition to hemorrhage. These responses are emerging as potentially important determinants of the severity of the tissue injury response, and there is growing clinical evidence that they are predictive of clinical outcome following reperfusion therapy. This review provides a summary of animal studies that have focused on the mechanisms that may underlie the genesis of no-reflow and hemorrhage following reperfusion of ischemic tissues, and addresses the clinical evidence that implicates these vascular events in the responses of the ischemic brain (stroke) and heart (myocardial infarction) to reperfusion therapy. Inasmuch as reactive oxygen species (ROS) and matrix metalloproteinases (MMP) are frequently invoked as triggers of the microvascular dysfunction elicited by I/R, the potential roles and sources of these mediators are also discussed. The available evidence in the literature justifies the increased interest in the development of no-reflow and hemorrhage in heart and brain following reperfusion therapy, and suggests that these vascular events may be predictive of poor clinical outcome and warrant the development of targeted treatment strategies.