title: Detailed characterization of a long-term rodent model of critical illness and recovery.
abstract: OBJECTIVE
  To characterize a long-term model of recovery from critical illness, with particular emphasis on cardiorespiratory, metabolic, and muscle function.
  
  
  METHODS
  Randomized controlled animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male Wistar rats.
  
  
  METHODS
  Intraperitoneal injection of the fungal cell wall constituent, zymosan or n-saline.
  
  
  RESULTS
  Following intervention, rats were followed for up to 2 weeks. Animals with zymosan peritonitis reached a clinical and biochemical nadir on day 2. Initial reductions were seen in body weight, total body protein and fat, and muscle mass. Leg muscle fiber diameter remained subnormal at 14 days with evidence of persisting myonecrosis, even though gene expression of regulators of muscle mass (e.g., MAFbx, MURF1, and myostatin) had peaked on days 2-4 but normalized by day 7. Treadmill exercise capacity, forelimb grip strength, and in vivo maximum tetanic force were also reduced. Food intake was minimal until day 4 but increased thereafter. This did not relate to appetite hormone levels with early (6 hr) rises in plasma insulin and leptin followed by persisting subnormal levels; ghrelin levels did not change. Serum interleukin-6 level peaked at 6 hours but had normalized by day 2, whereas interleukin-10 remained persistently elevated and high-density lipoprotein cholesterol persistently depressed. There was an early myocardial depression and rise in core temperature, yet reduced oxygen consumption and respiratory exchange ratio with a loss of diurnal rhythmicity that showed a gradual but incomplete recovery by day 7.
  
  
  CONCLUSIONS
  This detailed physiological, metabolic, hormonal, functional, and histological muscle characterization of a model of critical illness and recovery reproduces many of the findings reported in human critical illness. It can be used to assess putative therapies that may attenuate loss, or enhance recovery, of muscle mass and function.
authors.affiliation: 1Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, United Kingdom. 2Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, United Kingdom. 3Section of Investigative Medicine, Imperial College London, London, United Kingdom. 4Division of Neuropathology, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, United Kingdom. 5Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom. 6Dubowitz Neuromuscular Centre and MRC Centre for Neuromuscular Disorders, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, United Kingdom. 7Laboratoire de Physiologie de l'Exercice, Université de Lyon, Saint Etienne, France. 8Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Hill
authors.forename: Saima
authors.initials: S
authors.lastname: Saeed
authors.forename: Rahul
authors.initials: R
authors.lastname: Phadke
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Darren
authors.initials: D
authors.lastname: Chambers
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Wilson
authors.forename: Josiane
authors.initials: J
authors.lastname: Castells
authors.forename: Jerome
authors.initials: J
authors.lastname: Morel
authors.forename: Damien G
authors.initials: DG
authors.lastname: Freysennet
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Brett
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Murphy
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
mesh_terms: D000818:Animals; D001835:Body Weight; D016638:Critical Illness; D004195:Disease Models, Animal; D002149:Energy Intake; D005080:Exercise Test; D005223:Fats / Q000378:metabolism; D018737:Hand Strength; D006334:Heart Function Tests; D007378:Interleukins / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005223:Fats; D007378:Interleukins; D008055:Lipids; D011506:Proteins