title: Reduced skeletal muscle function is associated with decreased fiber cross-sectional area in the Cy/+ rat model of progressive kidney disease.
abstract: BACKGROUND
  The combination of skeletal muscle wasting and compromised function plays a role in the health decline commonly observed in chronic kidney disease (CKD) patients, but the pathophysiology of muscle mass/strength changes remains unclear. The purpose of this study was to characterize muscle properties in the Cy/+ rat model of spontaneously progressive CKD.
  
  
  METHODS
  Leg muscle function and serum biochemistry of male Cy/+ (CKD) rats and their nonaffected littermates (NLs) were assessed in vivo at 25, 30 and 35 weeks of age. Architecture and histology of extensor digitorum longus (EDL) and soleus (SOL) muscles were assessed ex vivo at the conclusion of the experiment. We tested the hypothesis that animals with CKD have progressive loss of muscle function, and that this functional deficit is associated with loss of muscle mass and quality.
  
  
  RESULTS
  Thirty-five-week-old CKD rats produced significantly lower maximum torque in ankle dorsiflexion and shorter time to maximum torque, and longer half relaxation time in dorsiflexion and plantarflexion compared with NL rats. Peak dorsiflexion torque (but not plantarflexion torque) in CKD remained steady from 25 to 35 weeks, while in NL rats, peak torque increased. Mass, physiologic cross-sectional area (CSA) and fiber-type (myosin heavy chain isoform) proportions of EDL and SOL were not different between CKD and NL. However, the EDL of CKD rats showed reduced CSAs in all fiber types, while only MyHC-1 fibers were decreased in area in the SOL.
  
  
  CONCLUSIONS
  The results of this study demonstrate that muscle function progressively declines in the Cy/+ rat model of CKD. Because whole muscle mass and architecture do not vary between CKD and NL, but CKD muscles show reduction in individual fiber CSA, our data suggest that the functional decline is related to increased muscle fiber atrophy.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Organ
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Srisuwananukorn
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Price
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jeffery E
authors.initials: JE
authors.lastname: Joll
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Biro
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Rupert
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.affiliation: Department of Physical Therapy, Indiana University School of Health and Rehabilitation Science, Indianapolis, IN, USA.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Avin
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA Roudebush Veterans Affairs Medical Center, Indianapolis, IN, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Allen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D018995:Myosin Heavy Chains / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018995:Myosin Heavy Chains
keywords: atrophy; chronic kidney disease; muscle function; muscle quality; rat models