Understanding Exercise (in)tolerance in Sickle Cell Disease: Impacts of Hemolysis and Exercise Training on Skeletal Muscle Oxygen Delivery,2024, Irwin

Abstract
Sickle cell disease (SCD) is characterized by central (cardiac) and peripheral vascular dysfunctions, significantly diminishing exercise capacity and quality of life. While central cardiopulmonary abnormalities in SCD are known to reduce exercise capacity and quality of life; the impact of hemolysis and subsequent cell-free hemoglobin (Hb)-mediated peripheral vascular abnormalities on those outcomes are not fully understood.

Despite the recognized benefits of exercise training for cardiovascular health and clinical management in chronic diseases like heart failure, there remains substantial debate on the advisability of regular physical activity for SCD patients. This is primarily due to concerns that prolonged and/or high-intensity exercise might trigger metabolic shifts leading to vaso-occlusive crises.

As a result, exercise recommendations for SCD patients are often vague or nonexistent, reflecting a gap in knowledge about the mechanisms of exercise intolerance and the impact of exercise training on SCD-related health issues.

This mini-review sheds light on recent developments in understanding how SCD affects exercise tolerance, with a special focus on the roles of hemolysis and the release of cell-free hemoglobin in altering cardiovascular and skeletal muscle function. Also highlighted here is the emerging research on the therapeutic effects and safety of exercise training in SCD patients. Additionally, the review identifies future research opportunities to fill existing gaps in our understanding of exercise (in)tolerance in SCD.

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Diseases, and particularly infections, that attack red blood cells are, I think, more common than most people appreciate. Since impaired skeletal muscle function is at play in many such cases, perhaps there is a subset of pwME that may be impacted.

 

This is particularly interesting because it is about after-effects ie what exercise can trigger later as a cascade?

 

Add bartonella (have a cat?) and babesiosis (take walks in parks or woods?) to that list, at least potentially.

 

If cells are less deformable, it reduces the ability to supply oxygen to tissues in the body. It doesn't effectively allow cells to perform their function to oxygenate tissues, cells needs to undergo significant deformation and be able to elastically recover to their original shapes.
RBC deformability is already already quantifiable measurement that is an established biomarker for some diseases, including sickle cell anemia and malaria . These two conditions are characterized by decreased RBC deformability and have some symptoms in common with CFS. RBCs are also known to be less deformable after storage outside the body for prolonged periods of time.

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My understanding is that symptoms of exercise intolerance occur immediately after exercise?

 

This is the second potentially relevant sickle cell paper I've sen this week, I posted the other one here: https://www.s4me.info/threads/less-...-disease-caruso-et-al-2024.39940/#post-550623

I've emailed the corresponding author to try to get a fulltext version of this. Will post here if he sends it.

 

I've DM'ed you @Murph

 

Cardiac diastolic maladaptation is associated with the severity of exercise intolerance in SCA patients, 2024, Thomas d'Humieres et al

Conclusion and perspectives
This pilot study provides a new understanding of the mechanisms associated with exercise limitation in SCA patients, adding the role of impaired cardiac diastolic function to anemia. Integrative, sub-maximal, lactate driven exercise evaluation could be safely used to stratify the severity of SCA patients by revealing latent heart impairment or significant metabolic vulnerability and could be the starting point for reinforced therapies and rehabilitation programs.


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