N-acetyl cysteine pre-treatment attenuates inflammatory changes in the warm ischemic murine lung

J Heart Lung Transplant. 2007 Dec;26(12):1326-32. doi: 10.1016/j.healun.2007.09.008.

Abstract

Background: The warm ischemic period in non-heart-beating donor lungs may contribute to a higher degree of ischemia-reperfusion injury after lung transplantation. We investigated the impact and timing of administration of N-acetyl cysteine (NAC) on inflammatory parameters.

Methods: Ischemia (I) was induced by clamping the hilum of the left lung for 90 minutes, and some protocols were followed by reperfusion (R) for 4 hours. Mice were divided into nine groups (n = 6/group): three control groups ([sham] (thoracotomy only), [I] and [I+R]); two groups with saline instillation only ([saline+I] and [saline+I+R]); and four experimental groups with NAC (50 mg/kg), administered by instillation ([NAC+I], [NAC+I+R] and [I+NAC+R]) or by aerosol ([NACaero+I+R]). Cell counts and protein levels in bronchoalveolar lavage (BAL) were determined.

Results: NAC administered prior to hilar clamping led to a significant decrease in macrophages and lymphocytes and interleukin (IL)-1 beta levels after ischemia. NAC also resulted in significantly fewer macrophages, lymphocytes and neutrophils as well as IL-1 beta, keratinocyte cytokine (KC), monocyte chemoattractant protein (MCP)-1 and IL-6 levels in BAL taken after reperfusion.

Conclusions: NAC treatment prior to warm ischemia attenuates inflammatory changes after both the ischemic and reperfusion periods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Animals
  • Biopsy
  • Bronchoalveolar Lavage
  • Cell Count
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Free Radical Scavengers / therapeutic use*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Leukocytes / pathology
  • Lung / metabolism
  • Lung / pathology*
  • Lung Transplantation / methods
  • Lung Transplantation / pathology*
  • Lymphocytes / pathology
  • Macrophages / pathology
  • Mice
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Warm Ischemia / adverse effects*

Substances

  • Chemokines
  • Cytokines
  • Free Radical Scavengers
  • Intercellular Signaling Peptides and Proteins
  • Acetylcysteine