Muscle Function and Its Biological and Physiological Determinants in Sickle Cell Disease

Muscle Function and Its Biological and Physiological Determinants in Sickle Cell Disease

Background : Sickle cell patients have profound remodeling of their muscle microcirculation networks with signs of amyotrophy. However, the consequences of these muscle alterations on the functional status of muscles are unknown. In addition, whether the poor physical fitness of sickle cell patients can be attributed, at least partly, to an hypothetical muscle dysfunction has never been tested.

Purpose : this study will compare the muscle function of legs between sickle cell patients (SS and SC genotypes) and healthy individuals (AA genotype) before, during and after a short localized muscle endurance exercise.

Abstract : Very recently, a study reported large differences between the muscle microcirculation networks of sickle cell patients compared to healthy individuals with decreased capillary density and higher proportion of large capillaries in the former population. In addition, the same study showed signs of amyotrophy in sickle cell patients. However, the muscle function of sickle cell patients has not been investigated and one may suggest that muscle dysfunction could participate in the decrease of physical fitness, in association with the hematological and hemorheological disorders, already reported in this population. The hypothesis is that muscle fatigue during a short localized muscle endurance exercise should be higher in sickle cell patients compared to healthy individuals, due to a greater recruitment of glycolytic fibers and a faster decrease of muscle oxygenation during exercise.

Inclusion Criteria:

For Sickle cell patients :

• age ≥ 15 and < 60 years old,
• SS homozygote or SC heterozygote
• in clinical steady state (i.e. without vaso-occlusive crisis or recent blood transfusion)
• identified by systematic neonatal screening programs,
• registered in the French medical social security national program

For Healthy and non sickle cell subjects:

• age ≥ 18 and < 60 years old
• without cardiovascular/respiratory/muscle disease,
• registered in the French medical social security national program.

Exclusion Criteria:

• other hemoglobinopathies,
• stroke or vasculopathy history,
• presence of leg ulcers or osteonecrosis,
• recent infectious episode (less than 1 month),
• chronic transfusion therapy programs,
• recent blood transfusion or phlebotomies (less than 3 months),
• patients not at steady state,
• pregnancy or breast feeding