Exacerbated metabolic changes in skeletal muscle of sickle cell mice submitted to an acute ischemia-reperfusion paradigm.

ABSTRACT

Sickle cell disease (SCD) is characterized by painful vaso-occlusive crisis. While there are several metabolic abnormalities potentially associated with muscular ischemia-reperfusion cycles that could be harmful in the context of SCD, the metabolic consequences of such events are still unknown. Ten controls (HbAA), thirteen heterozygous (HbAS), and ten homozygous (HbSS) SCD mice were submitted to a standardized protocol of rest-ischemia-reperfusion of the left leg during which adenosine triphosphate, phosphocreatine, and inorganic phosphate concentrations as well as intramuscular pH were measured using phosphorous magnetic resonance spectroscopy (MRS). Forty-eight hours later, skeletal muscles were harvested. Oxidative stress markers were then measured on the tibialis anterior. At the end of the ischemic period, HbSS mice had a lower pH value as compared with the HbAA and HbAS groups (P<0.01). During the reperfusion period, the initial rate of phosphocreatine resynthesis was lower in HbSS mice as compared with HbAA (P<0.05) and HbAS (P<0.01) animals. No significant difference among groups was observed regarding oxidative stress markers. HbSS mice displayed a higher intramuscular acidosis during the ischemic period while their mitochondrial function was impaired as compared with their HbAA and HbAS counterparts. These metabolic abnormalities could worsen the complications related to the pathology of SCD.