title: Neuromuscular Recovery Is Prolonged After Immobilization or Superimposition of Inflammation With Immobilization Compared to Inflammation Alone: Data From a Preclinical Model.
abstract: OBJECTIVE
  Recovery from ICU-acquired muscle weakness extends beyond hospital stay. We hypothesized that immobilization, more than inflammation, plays a prominent role in the delayed recovery from critical illness.
  
  
  METHODS
  Prospective, randomized, controlled, experimental study.
  
  
  METHODS
  Animal laboratory, university hospital.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Animals were divided to have one hind limb immobilized (n = 129) or sham-immobilized (n = 129) on day -12. After surgery, rats were further assigned to two subgroups. To induce inflammation, rats received three IV injections of Corynebacterium parvum on days -12, -8, and -4. Controls received saline at the respective time-points. At day 0, the limbs were remobilized and recovery from inflammation and/or immobilization was followed for 36 days.
  
  
  RESULTS
  At day 0 and after 4, 12, or 36 days of recovery, maximum tetanic tension and tetanic fade (functional parameters = primary outcome variables) as well as nicotinic acetylcholine receptor expression, muscle mass, and histologic changes (structural parameters = secondary outcome variables) were measured. Impaired maximum tetanic tension, decreased tibialis muscle mass, and fiber diameter due to inflammation alone recovered by day 4. Tetanic fade was not affected by inflammation. Immobilization-induced loss of tibialis muscle mass, decreased fiber diameter, and tetanic fade did not return to normal until day 36, while maximum tetanic tension had recovered at that time. In the presence of inflammation and immobilization, the decrease in tibialis muscle mass, fiber diameter, and maximum tetanic tension, as well as decreased tetanic fade persisted until day 36. Up-regulation of nicotinic acetylcholine receptors normalized before day 4 following inflammation, but persisted until day 4 following immobilization.
  
  
  CONCLUSIONS
  In our model, muscle function and structure recovered from inflammation within 4-12 days. Immobilization-induced neuromuscular changes, however, persisted even at day 36, especially if inflammation was concomitant.
authors: 1Klinik für Anaesthesiologie, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. 2Department of Anesthesia and Critical Care, Shriners Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA.
authors: Christiane G
authors: CG
authors: Stäuble
authors: Marc
authors: M
authors: Helming
authors: J A Jeevendra
authors: JA
authors: Martyn
authors: Manfred
authors: M
authors: Blobner
authors: Heidrun
authors: H
authors: Fink
mesh_terms: D000818:Animals; D019417:Hindlimb Suspension / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D018908:Muscle Weakness / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology*; D011446:Prospective Studies; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D012032:Refractory Period, Electrophysiological / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D011978:Receptors, Nicotinic