title: Intestinal ischemia-reperfusion induced diaphragm contractility dysfunction: Electrophysiological and ultrastructural study in a neonatal rat model.
abstract: OBJECTIVE
  To evaluate the remote effect of intestinal ischemia reperfusion (IR) injury mediated by tumor necrosis factor alpha (TNF-α) on diaphragm contractility functions and whether administration of NAC may counteract the possible detrimental effects in an experimental neonatal rat model.
  
  
  METHODS
  40 Wistar rat pups were randomized into four groups; ten animals in each. Intestinal ischemia was conducted by obstructing mesentery of intestines by a silk loop. In the control group; only laparotomy was performed. After 1h ischemia, reperfusion was conducted for 1h in 1h group, 24h for 24h group and 24h for 24h+NAC group but administration of NAC (150mg/kg/day) intraperitoneally twice a day was performed. Inflammatory response was evaluated by tissue TNF-α level and contractility functions by mechanic activity studies of the diaphragm. Electrophysiology of the diaphragm and the phrenic nerve was conducted to determine neuropathy or myopathy and transmission electron microscopy was performed to evaluate ultrastructural changes in the phrenic nerve.
  
  
  RESULTS
  Diaphragm tissue TNF-α level significantly increased in 1h and 24h groups (P=0.004, P=0.0001; respectively). Diaphragm mechanic activation force and duration significantly decreased at 1h and 24h (P=0.004, P=0.02 and P=0.0001, P=0.0001; respectively). NAC administration significantly prevented decrease in the maximal contraction and the duration (P<0.001). Phrenic nerve compound action potential (CMAP) amplitude significantly decreased in 1h group (P<0.0001) and NAC administration significantly prevented this decrease when compared with 24h group (P<0.001). In diaphragmatic needle electromyography, the duration of motor unit potentials (MUP) was prolonged significantly when compared with control group. Contractility and electrophysiological studies were indicating primarily neuropathy in diaphragm dysfunction. Histopathology revealed axonal and myelin degeneration in the 1h and 24h group, but less injury in the NAC administered group.
  
  
  CONCLUSIONS
  Intestinal IR induced elevation of TNF-α level in the diaphragm. Impairment in the diaphragm contractility and neuropathic changes in the phrenic nerve occurred even in the first hour of reperfusion. NAC administration prevented these detrimental effects.
authors.affiliation: Mersin University, School of Medicine, Department of Pediatric Surgery, Mersin, Turkey. Electronic address: hakantaskinlar@gmail.com.
authors.forename: Hakan
authors.initials: H
authors.lastname: Taşkınlar
authors.affiliation: Mersin University, School of Medicine, Department of Pediatric Surgery, Mersin, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Naycı
authors.affiliation: Mersin University, School of Medicine, Department of Biophysics, Mersin, Turkey.
authors.forename: Ülkü
authors.initials: Ü
authors.lastname: Çömelekoğlu
authors.affiliation: Mersin University, School of Medicine, Department of Biochemistry, Mersin, Turkey.
authors.forename: Gürbüz
authors.initials: G
authors.lastname: Polat
authors.affiliation: Çukurova University, School of Medicine, Department of Pathology, Adana, Turkey.
authors.forename: Suzan
authors.initials: S
authors.lastname: Zorludemir
authors.affiliation: Mersin University, School of Medicine, Department of Pediatric Surgery, Mersin, Turkey.
authors.forename: Dinçer
authors.initials: D
authors.lastname: Avlan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004576:Electromyography; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine
keywords: Diaphragm; Intestinal ischemia reperfusion; N-acetyl cysteine; Neuropathy; Phrenic nerve