title: Nebulized N-acetyl cysteine protects the pulmonary graft inside the non-heart-beating donor.
abstract: BACKGROUND
  The use of lungs from non-heart-beating donors (NHBD) might significantly alleviate the organ shortage. The tolerable warm ischemic period after cardiac arrest, however, is limited to approximately 1 hour. If the lung could be safely protected inside the cadaver, this time period may be prolonged. This would help to obtain family consent and to organize organ retrieval.
  
  
  METHODS
  Pigs (30.8 +/- 0.6 kg) were killed, left untouched for 3 hours, and divided into 3 groups. Nebulized N-acetyl cysteine (NAC) (300 mg), a precursor of the antioxidant agent glutathione, was administered during 10 minutes before death in Group I (NAC-NHBD, n = 6) and 15 minutes after death in Group II (NHBD-NAC, n = 6). In the control group, no aerosol was administered (NHBD, n = 6). After a warm ischemic interval of 3 hours, both lungs in all groups were topically cooled for 1 hour. Thereafter, the left lung was prepared for evaluation in an isolated reperfusion circuit. Hemodynamic, aerodynamic, and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. The right lung was used to measure reduced glutathione (GSH) and oxidized glutathione (GSSG) levels (micromol/g) in lung homogenates and total protein levels in bronchial lavage fluid.
  
  
  RESULTS
  Pulmonary vascular resistance, mean airway pressure, and W/D were significantly decreased in NAC-NHBD (1930 +/- 144 Dynes x sec x cm(-5), 14.2 +/- 0.5 cm H2O, and 7.4 +/- 0.4; p < 0.01, 0.01, and 0.05, respectively) and NHBD-NAC (1837 +/- 180 Dynes x sec x cm(-5), 13.3 +/- 1.2 cm H2O, and 7.3 +/- 0.3; p < 0.01, 0.05, and 0.05, respectively) when compared with the control group (5051 +/- 530 Dynes x sec x cm(-5), 17 +/- 0.4 cm H2O, 8.5 +/- 0.1, respectively). GSH/GSSG ratio was significantly higher and protein levels were significantly lower in NAC-NHBD (1.7 +/- 0.1 and 1315 +/- 60 microg/ml; p < 0.05 and 0.05, respectively) and NHBD-NAC (1.7 +/- 0.2 and 1475 +/- 159 microg/ml; p < 0.05 and 0.05, respectively) when compared with the control group (1.2 +/- 0.1 and 2150 +/- 200 microg/ml).
  
  
  CONCLUSIONS
  Nebulized NAC administered before or shortly after death attenuates early ischemia reperfusion injury via upregulation of glutathione. NAC might be a promising tool to protect the pulmonary graft from both controlled and uncontrolled NHBD.
authors.affiliation: Center for Experimental Surgery and Anesthesiology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Filip R
authors.initials: FR
authors.lastname: Rega
authors.forename: Wim A
authors.initials: WA
authors.lastname: Wuyts
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Jannis
authors.forename: Arne P
authors.initials: AP
authors.lastname: Neyrinck
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.forename: Toni E
authors.initials: TE
authors.lastname: Lerut
authors.forename: Dirk E M
authors.initials: DE
authors.lastname: Van Raemdonck
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000336:Aerosols; D000403:Airway Resistance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D016040:Lung Transplantation / Q000379:methods*; D009926:Organ Preservation / Q000379:methods*; D015424:Reperfusion; D034421:Sus scrofa; D013696:Temperature; D014655:Vascular Resistance
chemical_list: D000336:Aerosols; D016166:Free Radical Scavengers; D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine