Ischaemia‐induced muscle metabolic abnormalities are poorly alleviated by endurance training in a mouse model of sickle cell disease

New Findings

The aim of this study was to evaluate the potential beneficial effects of endurance training during an ischemia/reperfusion paradigm in sickle cell disease mice. Endurance training would not reverse the metabolic defects induced by a simulated vaso‐occlusive crisis in sickle cell mice, whether it is with regard to intramuscular acidosis, mitochondrial dysfunction or anatomical properties. Our results suggest that endurance training would reduce vaso‐occlusive crisis number rather than the complications related to vaso‐occlusive crisis.

Abstract

The aim of this study was to investigate whether endurance training could limit the abnormalities described in sickle cell disease (SCD) mice in response to an ischemia/reperfusion (I/R) paradigm. Ten sedentary (HbSS‐SED) and 9 endurance trained (HbSS‐END) SCD mice were submitted to a standardized protocol of I/R of the leg during which ATP, phosphocreatine and inorganic phosphate concentrations as well as intramuscular pH were measured using magnetic resonance spectroscopy. Forty‐eight hours later, skeletal muscles were harvested. Oxidative stress markers were then measured. While the time‐course of intramuscular pH was slightly different between trained and sedentary mice (p < 0.05), the extent of acidosis was similar at the end of the ischemic period. The initial rate of phosphocreatine resynthesis measured at blood flow restoration, illustrating mitochondrial function, was not altered in trained mice compared to sedentary mice. Although several oxidative stress markers were not different between groups (p > 0.05), the I/R‐related increase of uric acid concentration observed in sedentary SCD mice (p < 0.05) was not present in the trained group. The spleen weight, generally used as a marker of the severity of the disease, was not different between groups (p > 0.05). In conclusion, endurance training did not limit the metabolic consequences of an I/R paradigm in skeletal muscle of SCD mice, suggesting that the reduction in the severity of the disease previously demonstrated at the basal state would be attributable to a reduction of vaso‐occlusive crisis (VOC) occurrence rather than a decrease of the deleterious effects of VOC.

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