title: Iron supplementation effectively suppresses gastrocnemius muscle lesions to improve exercise capacity in chronic heart failure rats with anemia.
abstract: OBJECTIVE
  For patients with chronic heart failure (CHF), exertional fatigue is one of the most common and debilitating symptoms. However, the poor relationship between heart dysfunction and exercise capacity has been ascribed to peripheral abnormalities. Several previous studies confirmed that iron supplementation could significantly improve the exercise capacity of patients with CHF, although they did not analyze effects in the musculoskeletal system. The aim of this study was to investigate the effect of iron treatment on gastrocnemius muscles of CHF rats with anemia.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to coronary ligation to induce heart failure. At the same time, blood (1-1.5 mL) was withdrawn from the retro-orbital plexus once every week to induce anemia. After 6 wk of this process, iron dextran was administered to the CHF rats with anemia (CHFa rats) at the dose of 8, 16, 32, or 64 mg/kg every 2 d for 2 wk.
  
  
  RESULTS
  Iron dextran (8 mg/kg every 2 d) effectively improved hemodynamic parameters (P < 0.05) compared with CHFa rats. Similarly, this dose of iron dextran significantly reduced the ratio of heart weight to body weight (P < 0.01), whereas it significantly increased the distance run (m) to exhaustion (P < 0.01). Iron dextran effectively inhibited sarcoplasmic vacuolation and muscle atrophy of gastrocnemius muscles in CHFa rats, as evaluated by pathologic examinations. Other iron treatments, however, were found to be ineffective on the same parameters, so particular focus was placed on the iron dextran (8 mg/kg every 2 d) group in subsequent analyses. Consistently, phospho-p38 in gastrocnemius muscles of CHFa rats was markedly suppressed by iron dextran. Additionally, iron dextran significantly decreased c-fos and c-jun and up-regulated cellular FLICE-inhibitory protein expression levels.
authors.affiliation: Department of Physiology, School of Basic Medicine, Hebei College of Traditional Chinese Medicine, Hebei, China; The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Hebei Normal University, Hebei, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guan
authors.affiliation: Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Mu-Qing
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Hebei Normal University, Hebei, China.
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Basic Medicine, Hebei College of Traditional Chinese Medicine, Hebei, China.
authors.forename: Wen-Ya
authors.initials: WY
authors.lastname: Li
authors.affiliation: Department of Physiology, School of Basic Medicine, Hebei College of Traditional Chinese Medicine, Hebei, China. Electronic address: wangna9503@126.com.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
mesh_terms: D000740:Anemia / Q000097:blood / Q000150:complications / Q000178:diet therapy*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D002908:Chronic Disease; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000178:diet therapy* / Q000209:etiology / Q000378:metabolism; D007501:Iron / Q000097:blood*; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010807:Physical Endurance / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D007505:Iron-Dextran Complex; D007501:Iron; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Anemia; Chronic heart failure; Exercise capacity; Gastrocnemius; Iron