Chronic tissue hypoxia as a possible driver of pathological alterations in Sickle cell disease

Background Sickle Cell Disease ( SCD) is an autosomal recessive disease due to the mutations in beta globin gene. It’s a disorder which is quite prevalent in Africa and the Mediterranean Region and has been associated with several chronic complications and comorbidities. Chronic tissue hypoxia could play a role in the pathophysiology of the complications associated with SCD. This study aimed to evaluate the relevance of chronic tissue hypoxia in SCD, using a skeletal muscle model. Method This is a cross-sectional study that compares SCD patients receiving optimal standard of care (SoC) to healthy controls in order to assess neuromuscular and clinical features. High density surface EMG signals were recorded from the vastus lateralis under isometric contraction at 60%(until exhaustion) of maximal voluntary force. The endurance level was estimated by time to task failure, average muscle fiber size was estimated by muscle fiber conduction velocity (MFCV) and neural drive by motor unit firings.A 6MWT was carried out and quality of life (QoL) was assessed by FACIT-F scores. Result In total, 30 subjects (14 healthy, 16SCD) were admitted to the study. The median age was 25.5(range 18-63), 50% were males. The time to task failure was higher (P=0.569) in SCD (35.8±8.5) than in healthy controls(27.5±9.0) while the muscle fibre conduction velocity was lower (P=0.32) in SCD(4.9±0.3) than in healthy controls(5.1±0.5). The 6MWT was completed by all subjects. The total distance covered was higher(P=0.750) in SCD (522±66.7) than in healthy controls(514±57.3), There was a significant difference in the evaluation of quality of life using the FACIT-F score, the mean of total well- being in SCD patient was 107/160 and healthy control 136/160 (p=<0.001). Discussion SCD patients showed higher muscular endurance, while healthy controls showed higher muscular strength and higher muscle fiber. Overall, no statistical significance were noted in these measurements. However, the lower muscle fibre in SCD patients may be attributed to decreased physical activities and the higher muscular endurance to increased tolerance to pain. Due to the results obtained, chronic tissue hypoxia may not be a possible significant contributor to the burden of the disease.