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

Sickle cell disease (SCD) is characterized by painful vaso-occlusive crises. While there are several metabolic abnormalities potentially associated with muscular ischemia - reperfusion cycles which could be harmful in the context of SCD, the metabolic consequences of such events are still unknown. Ten controls (HbAA), 13 heterozygous (HbAS) and 10 homozygous (HbSS) SCD mice were submitted to a standardized protocol of rest - ischemia - reperfusion of the right leg during which ATP, 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 to the HbAA (p < 0.01) and HbAS groups (p < 0.01). During the reperfusion period, the initial rate of phosphocreatine resynthesis was lower in HbSS mice compared to 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 to their HbAA and HbAS counterparts. These metabolic abnormalities could worsen the complications related to the pathology of SCD.
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research