Is Skeletal Muscle Dysfunction a Limiting Factor of Exercise Functional Capacity in Patients with Sickle Cell Disease?

Etienne Gouraud,Céline Renoux,Camille Faes,Salima Merazga,Camille Boisson,Arnaud Hot,Alexandra Gauthier-Vasserot,Solène Poutrel,Christophe Hautier,Giovanna Cannas,Yves Bertrand,Philippe Joly,Philippe Connes

doi:10.3390/jcm10112250

Abstract

Patients with sickle cell disease (SCD) have reduced functional capacity due to anemia and cardio–respiratory abnormalities. Recent studies also suggest the presence of muscle dysfunction. However, the interaction between exercise capacity and muscle function is currently unknown in SCD. The aim of this study was to explore how muscle dysfunction may explain the reduced functional capacity. Nineteen African healthy subjects (AA), and 24 sickle cell anemia (SS) and 18 sickle cell hemoglobin C (SC) patients were recruited. Maximal isometric torque (Tmax) was measured before and after a self-paced 6-min walk test (6-MWT). Electromyographic activity of the Vastus Lateralis was recorded. The 6-MWT distance was reduced in SS (p < 0.05) and SC (p < 0.01) patients compared to AA subjects. However, Tmax and root mean square value were not modified by the 6-MWT, showing no skeletal muscle fatigue in all groups. In a multiple linear regression model, genotype, step frequency and hematocrit were independent predictors of the 6-MWT distance in SCD patients. Our results suggest that the 6-MWT performance might be primarily explained by anemia and the self-paced step frequency in SCD patients attempting to limit metabolic cost and fatigue, which could explain the absence of muscle fatigue.

Highlights

The 6-min walk test (6-MWT) did not result in skeletal muscle fatigue as shown by to test if genotype, step frequency, Tmax and/or hematocrit were independent predictors the absence of significant reduction in Tmax and/or modification in the root mean squared (RMS) value during of the 6-MWT distance
The 6-MWT did not result in skeletal muscle fatigue as shown by the absence of significant reduction in Tmax and/or modification in the RMS
Our results showed that skeletal muscle dysfunction would be implicated in the reduced functional capacity of sickle cell disease (SCD) patients, especially in SS, even though the

Summary

Introduction

Sickle cell disease (SCD) is a group of genetic disorders characterized by the presence of at least one hemoglobin S (HbS) allele (p.Glu7Val in the hemoglobin β globin-subunit) and a second β globin-subunit pathogenic variant, resulting in pathological hemoglobin polymerization [1]. The most prevalent form of SCD is the homozygous sickle cell anemia (SS), where patients inherit two copies of HbS [2]. HbS is able to polymerize, creating rigid fibers that modify the morphology of the red blood cells (RBCs) into a crescent-like shape (i.e., sickling) [3]. Association of the HbS allele with the hemoglobin C (HbC) allele (p.Glu7Lys in β globin-subunit) leads to sickle cell-hemoglobin

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