Exacerbated in vivo metabolic changes suggestive of a spontaneous muscular vaso-occlusive crisis in exercising muscle of a sickle cell mouse

Abstract

, Exacerbated in vivo metabolic changes suggestive of a spontaneous muscular vasoocclusive crisis in exercising muscle of a sickle cell mouse, Blood Cells, Molecules and Diseases (2017), doi: 10.1016/j.bcmd.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTA C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P TMuscular vaso-occlusive crisis in a sickle mouse 3 AbstractWhile sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of restexercise -recovery at two different intensities in ten SCD mice. Among these mice, one single mouse presented divergent responses. A statistical analysis (based on confidence intervals) revealed that this single mouse presented slower phosphocreatine resynthesis and inorganic phosphate disappearance during the post-stimulation recovery of one of the protocols, what could suggest an ischemia. This study described, for the first time in a sickle cell mouse in vivo, exacerbated metabolic changes triggered by an exercise session that would be suggestive of a live observation of a muscular VOC. However, no evidence of a direct cause-effect relationship between exercise and VOC has been put forth. Key wordsPhysical activity, red blood cell sickling, HbS polymerization, magnetic resonance spectroscopy of phosphorus 31. ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P TMuscular vaso-occlusive crisis in a sickle mouse 4 Introduction Sickle cell disease (SCD) is a genetic hemoglobinopathy related to the production of abnormal hemoglobin (HbS). In its deoxygenated form, HbS tends to polymerize, leading to the sickling of red blood cells (RBC) [1]. Owing to their poor deformability and elevated adhesion, sickle RBCs tend to obstruct the microcirculation thereby leading to vaso-occlusive crises (VOC) that represent the most severe clinical complications of SCD [2]. If this type of crisis has been acknowledged in many tissues [2], the potential occurrence of such an event in skeletal muscle has rarely been documented [3; 4; 5; 6]. To the best of our knowledge, no direct observation of a skeletal muscle VOC has been performed in real time.In a pr...

The alterations effects in phosphorus of erythropoietin and U-74389G

“…Yuan, et al analyzed [17] the effects of surgical total removal of parathyroid gland (PTG) tissue in rats. Chatel, et al used [18] magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations throughout two standardized protocols of a spontaneous muscular vaso-occlusive crisis in restexercise -recovery at two different intensities in sickle cell disease (SCD) mice. Němcová A, et al found enabled [19] phosphorus magnetic resonance spectroscopy ( 31 P MRS) to evaluate oxidative muscle impaired metabolism in patients with complicated diabetes.…”