Effect of N-acetyl-L-cysteine on lung ischaemia reperfusion injury in a porcine experimental model

ANZ J Surg. 2008 Jan-Feb;78(1-2):72-7. doi: 10.1111/j.1445-2197.2007.04357.x.

Abstract

Background: The purpose of the present study was to investigate the effect of N-acetyl-L-cysteine on lung ischaemia reperfusion injury.

Methods: Nineteen pigs were used. Group I (n = 5) underwent sham operation, group II (n = 7) 90-min left-lung ischaemia followed by 180-min reperfusion. In group III (n = 7) N-acetyl-l-cysteine was given (160 mg/kg) during ischaemia into the pulmonary artery. Lung-functional and haemodynamic parameters were measured; serum and lung tissue samples were obtained and analysed for interleukin-10 and tumour necrosis factor-alpha. At the end of the reperfusion bronchoalveolar lavage was carried out from the ipsilateral lung and analysis for total protein, phospholipase-A(2) and platelet-activating factor acetylhydrolase was carried out. Histological specimens were graded (0-3) for alveolar oedema, interstitial thickening and leucocyte infiltration. Statistical analysis was by means of one-way analysis of variance and Kruskal-Wallis test.

Results: There were no differences in haemodynamic parameters, serum and tissue interleukin-10 and tumour necrosis factor-alpha. Pulmonary compliance was decreased in groups II and III (P = 0.002 and P = 0.001, respectively) during ischaemia and reperfusion. Pulmonary vascular resistance was increased in group II (P = 0.051) during reperfusion. In group III total protein and platelet-activating factor acetylhydrolase were increased (P = 0.004 and P = 0.006, respectively) and phospholipase-A(2) was reduced (P = 0.002), indicating an indirect surfactant-protective effect. Interstitial thickening was excessive in group II (P = 0.001); however, alveolar oedema was reduced (P = 0.002) when compared with group III.

Conclusion: N-acetyl-L-cysteine when administered directly in the pulmonary artery showed no significant change in haemodynamic and functional lung parameters during ischaemia reperfusion; it does, however, have an indirect surfactant-protective effect.

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / therapeutic use*
  • Animals
  • Disease Models, Animal
  • Free Radical Scavengers / administration & dosage
  • Free Radical Scavengers / therapeutic use*
  • Infusions, Intra-Arterial
  • Interleukin-10 / metabolism
  • Lung Compliance / physiology
  • Phospholipases A2 / metabolism
  • Platelet Activating Factor / metabolism
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Swine
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Resistance / physiology

Substances

  • Free Radical Scavengers
  • Platelet Activating Factor
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Phospholipases A2
  • Acetylcysteine