The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS; 2022, Kell

[SNT Gatchaman]

The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications
Kell DB, Pretorius E

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.

PubMed | PDF (Biochem J)

 

[SNT Gatchaman]

Looks like another overview paper, hypothesising that impaired perfusion and oxidative stress are at the centre of chronic illness.

A considerable number of chronic disorders or syndromes seem to occur following the acute stages of an infection [...]. They are characterised by a multiplicity of symptoms, that, [...] also exhibit two particular features: (i) a variety of manifestations of exceptional levels of fatigue [...] and (ii) episodic disability, i.e. periods of unwellness that are relatively benign interspersed with periods (‘relapses’ or ‘crashes’) characterised by acute, severe, and often debilitating symptoms. Another striking feature of these diseases is that they predominantly affect women.

By and large, these diseases (especially ME/CFS and Long COVID) have not been well managed because their aetiologies have been uncertain and even their organic (rather than psychological) nature has been questioned. Some of the management practices, such as graded exercise therapy, have even been harmful, especially since post-exertional malaise (PEM) (a worsening of symptoms following exertion) is even a hallmark of such diseases. Indeed, we consider (and argue) that periodic ischaemia–reperfusion injury is largely responsible for the relapsing observed.

 

[RedFox]

Every time someone claims they found a connection between two rather different diseases, I tend to be skeptical. While I'm generally a fan of Resia Pretorius's work, this doesn't excite me much.

 

[Amw66]

PhD Research into ischaematic reperfusion ( funded by heart research- this is the west of Scotland ) was being done at Glasgow uni years ago. Looking at impacts on mitochondria amongst other aspects as precursor to drug development.
I don't know where it went in terms of results.
My daughter spent months in a lab as part of her undergraduate thesis trying to devise a molecular probe that worked.
Richard Hartley was her prof : ROS , inflammation and mitochondria are some of his particular interests ( as well as distilling gin )

How do we get other disciplines / researchers interested? There are so many potential aspects that could link into research being done for other conditions ....

 

[Sly Saint]

Prof Douglas Kell, Research Chair in Systems Biology, University of Liverpool
Post-exertional malaise as a Chronic Ischaemia-Reperfusion injury in Long COVID and M.E./CFS resulting from fibrin amyloid micro clots.

 

[Jonathan Edwards]

I am afraid that to me this sounds like exactly the same handwaving speculation I was familiar with in the 1980s. I cannot seriously believe it makes any sense. Dragging up reperfusion injury and oxidative stress and recommending anti-oxidants seems a bit like recommending people wear bell-bottom trousers again.

Again we see diagrams with no precise mechanism - just arrows sort of going this way or that.