Intestinal ischemia-reperfusion induced diaphragm contractility dysfunction: Electrophysiological and ultrastructural study in a neonatal rat model

AimTo 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.Methods40 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 1 h ischemia, reperfusion was conducted for 1 h in 1 h group, 24 h for 24 h group and 24 h for 24 h + NAC group but administration of NAC (150 mg/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.ResultsDiaphragm tissue TNF-α level significantly increased in 1 h and 24 h groups (P = 0.004, P = 0.0001; respectively). Diaphragm mechanic activation force and duration significantly decreased at 1 h and 24 h (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 1 h group (P < 0.0001) and NAC administration significantly prevented this decrease when compared with 24 h 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 1 h and 24 h group, but less injury in the NAC administered group.ConclusionsIntestinal 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.