Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.

中文翻译：

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缺血再灌注损伤在类风湿性关节炎、Long COVID 和 ME/CFS 等慢性复发性疾病中的潜在作用：证据、机制和治疗意义。

缺血再灌注 (IR) 损伤是由在缺氧后的再氧合阶段产生的活性氧物质爆发引发的，在各种急性情况下是众所周知的。我们在此争辩说，IR 损伤也是多种慢性炎症性疾病的病理学要素的基础，包括类风湿性关节炎、ME/CFS 以及我们的主要关注点和最近的 Long COVID。局部缺血可能通过毛细血管的纤维蛋白淀粉样蛋白微凝块阻塞引起，例如在运动开始时；再灌注是完成后的必然结果。我们在这里排练这些事件的机制证据，就其表现为氧化应激、过度炎症、肥大细胞活化、标志物代谢物的产生和相关活动而言。这种基于微凝块的现象可以解释在这些条件下可能观察到的呼吸困难/疲劳和运动后不适，以及许多其他可观察到的现象。对这些过程的认识在机械上意味着治疗益处可能来自抗氧化剂、抗炎剂、铁螯合剂，以及通过合适的、安全的纤维蛋白溶解剂和/或抗凝血剂。我们回顾了与此一致的大量现有证据，以及所涉及的生化机制。和通过合适的、安全的纤维蛋白溶解剂和/或抗凝血剂。我们回顾了与此一致的大量现有证据，以及所涉及的生化机制。和通过合适的、安全的纤维蛋白溶解剂和/或抗凝血剂。我们回顾了与此一致的大量现有证据，以及所涉及的生化机制。