N-acetyl cysteine attenuates the inflammatory response in warm ischemic pig lungs

J Surg Res. 2008 May 15;146(2):177-83. doi: 10.1016/j.jss.2007.05.018. Epub 2007 Jul 20.

Abstract

Background: Lungs donated after cardiac death (DCD) may significantly reduce current organ shortage. However, the warm ischemic period following circulatory arrest may enhance ischemia-reperfusion injury (IRI). We investigated the possible therapeutic effect of N-acetyl cysteine (NAC), a potent anti-oxidative agent on IRI in a porcine ex vivo lung reperfusion model.

Materials and methods: NAC (50 mg/kg) was nebulized to pigs (n = 6/group) prior to sacrifice (NAC-DCD). In DCD-NAC, animals received NAC 15 min after death. Control animals did not receive an aerosol (DCD). Interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-8, lactate dehydrogenase activity and thiobarbituric acid reactive substances were measured and cells were counted in broncho-alveolar lavage from the right lung after a 3-h warm plus 1-h cold ischemic interval.

Results: There were no differences in cells between groups, however cell death was lower in NAC-DCD (10.3 +/- 1.5%) and DCD-NAC (7.83 +/- 1.8%) compared to DCD (18.0 +/- 3.8%). IL-1beta levels (111.5 +/- 28.8 pg/mL and 92.2 +/- 51.0 pg/mL versus 250.3 +/- 56.6 pg/mL) and lactate dehydrogenase activity (1258.0 +/- 440.9 U/L and 1606.0 +/- 289.0 U/L versus 2848.0 +/- 760.9 U/L) were significantly lower in NAC-DCD and DCD-NAC compared with DCD, respectively. These postischemic inflammatory markers correlated with functional parameters upon reperfusion of the left lung, reported in a previous study.

Conclusions: Administration of NAC prior to or shortly after circulatory arrest results in a marked reduction of inflammation during the warm ischemic phase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Antioxidants / pharmacology*
  • Disease Models, Animal
  • Inflammation / drug therapy
  • Ischemia
  • Lung / blood supply
  • Lung / drug effects*
  • Lung Transplantation
  • Organ Preservation / methods*
  • Reperfusion Injury / drug therapy*
  • Swine
  • Temperature

Substances

  • Antioxidants
  • Acetylcysteine