Hemorheological responses to an acute bout of maximal exercise in Veterans with Gulf War Illness, 2021, Wei Qian et al

[Mij]

Abstract
Background
Altered red blood cell (RBC) deformability has been reported in Veterans with Gulf War Illness (GWI) who endorse exercise-induced symptom exacerbation and fatigue. However, it is unknown whether altered RBC deformability is worsened secondary to exercise.

Objective
To evaluate RBC deformability in response to maximal exercise in individuals with and without GWI.

Methods
Seventeen Veterans with GWI and 11 controls performed maximal exercise and provided blood samples (pre-, immediately post- and 60-min post-exercise). We calculated RBC deformation at infinite stress (EIMAX), shear stress for half-deformation (SS1/2) and their ratio (SS1/2/EIMAX) via repeated measures ANOVA with group and time as factors.

Results
A moderate interaction effect (p = 0.08, η2p = 0.10), large main effect for group (p = 0.02, η2p = 0.19) and moderate main effect for time (p = 0.20, η2p = 0.06) were observed for EIMAX, but only the main effect for group reached statistical significance. Changes in SS1/2 and SS1/2/EIMAX over time were similar between cases and controls as were main effects.

Conclusions
Veterans with GWI had more deformable RBCs in comparison to controls that was unaffected by maximal exercise. Future studies to confirm our findings and identify associated mechanisms are warranted.

https://www.sciencedirect.com/science/article/pii/S0024320521007001?via=ihub

 

[SNT Gatchaman]

An edited quote from discussion, my bolding.

In our prior study, we acknowledged that increased deformability among Veterans with GWI appears counterintuitive as greater deformability is typically associated with improved circulation and health benefits. As previously noted, there are negative consequences of RBCs becoming too deformable – i.e., increased pulmonary capillary transit times and reduced oxygen binding – as well as the positive association between deformability and RBC size in patients with macrocytosis.

The latter finding supports our hematological findings suggesting greater heterogeneity in RBC populations among Veterans with GWI (i.e., increased red cell distribution width [RDW]), which we have discussed previously. It should be noted that RBC profiles characterized by greater heterogeneity, increased RDW, has also been reported in ME/CFS and identified as a primary factor distinguishing patients from controls.

In comparison to ME/CFS, studies have reported either no change or decreased deformability in patients with ME/CFS relative to controls. Using ektacytometry similar to the present study, Brenu et al. did not observe a statistically significant difference between patients with ME/CFS (n = 6) relative to controls (n = 6); although, EIMAX was larger (not statistically significant) in patients with ME/CFS which is consistent with our findings. In contrast, Saha et al. reported less deformable RBCs among patients with ME/CFS (n = 16) relative to controls.

This study, however, utilized a custom microfluidic platform that assesses RBC deformability on an individual cell basis using a cell transit strategy as opposed to ektacytometry that utilizes populational analysis. As previously noted, there appears great heterogeneity in RBC populations for both individuals with GWI and ME/CFS as reflected by increased RDW. This observation likely has implications that impact the interpretation of the individual cell (i.e., microfluidic) and population (i. e., ektacytometry) analysis that are not yet fully appreciated but deserving of additional attention.

Although inconsistent findings across ME/CFS and the present study may be attributed in part to differences in techniques to assess deformability, there remain important distinctions between ME/CFS and GWI such as the greater number of women affected with ME/CFS that likely contribute to these findings. Additionally, the impact of exercise on RBC deformability in ME/CFS is presently unknown but warrants attention given the exercise-induced symptoms experienced by these individuals.

 

[SNT Gatchaman]

Probably hard to study, but I would like to know what happens to RBC deformability in the days following exercise in ME vs controls.

I suggest PEM results from acutely impaired red-cell deformability, due to the demands of increased flow through compromised micro-circulation. In principle this could work for exercise/muscles, cognition/brain, digestion/gut and might allow for the observed delayed onset of symptoms and variable time to recovery.

In many ways it's a shame I didn't have the researcher relationships and background knowledge I have now, back at the beginning of my illness. I did two treadmill tests for cardiac function. I would have happily tracked my RBCs over the following days for an n=1 evaluation of this question. I'm probably a bit more reluctant to risk this now, but maybe it's possible to show changes with more modest exercise challenges.

 

[hibiscuswahine]

First thought was smoking effects on their RBC deformity, mean Hb and RDW but they say they have analysed this and can put this aside as contributing.

@SNT Gatchaman - Need a fire sale at a lab, a few manuals and a shed, take your own blood and perhaps a step challenge, all for science.

 

[rvallee]

Very likely a stupid question but: could RBCs be so deformed they pretty clot themselves? As in the source of those micro-clots? Basically when they are squished through capillaries they clump together because they are so squishy, and maybe catch other things too. Probably not but it's nice to dream.

 

[Jonathan Edwards]

Very likely a stupid question but: could RBCs be so deformed they pretty clot themselves? As in the source of those micro-clots?

I think the micro clots came from cell free plasma fractions - i.e. no cells in them.
Squishiness would not encourage clotting. The squishier they are the faster the blood can move and the less likely it is to clot - since stasis is one of the things that encourages clotting.

I thought that previous work had suggested red cells might be stiffer in ME.