Role of inflammatory cells and adenosine in lung ischemia reoxygenation injury using a model of lung donation after cardiac death.
OBJECTIVE
The objective of this study is to analyze the role of inflammation in the lung ischemia reperfusion (IR) injury and determine the protective role of adenosine in an in vitro lung transplantation model.


METHODS
We used a hybrid model of lung donor after cardiac death, with warm ischemia in corpo of varying duration (2 h, 4 h) followed by in vitro lung slices culture for reoxygenation (1 h, 4 h and 24 h), in the presence or not of lymphocytes and of adenosine. To quantify the inflammatory lesions, we performed TNFα, IL2 assays, and histological analysis.


RESULTS
In this model of a nonblood perfused system, the addition of lymphocytes during reoxygenation lead to higher rates of TNFα and IL2 after 4 h than after 2 h of warm ischemia (P < .05). These levels increased with the duration of reoxygenation and were maximum at 24 h (P < .05). In the presence of adenosine TNFα and IL2 decreased. After 2 h of warm ischemia, we observed a significant inflammatory infiltration, alveolar thickening and a necrosis of the bronchiolar cells. After 4 h of warm ischemia, alveolar cells necrosis was associated.


CONCLUSIONS
This model showed that lymphocytes increased the inflammatory response and the histological lesions after 4 h of warm ischemia and that adenosine could have an anti-inflammatory role with potential reconditioning action when used in the pneumoplegia solution.
a Department of Thoracic and Cardio-Vascular Surgery , University Hospital of Rouen , Rouen , France.|b ABTE Toxemac, Rouen University , Rouen , France.
Hassiba
H
Smail
c Department of General and Thoracic Surgery , University Hospital of Rouen , Rouen , France.|d INSERM, Rouen University , Rouen , France.
Jean-Marc
JM
Baste
a Department of Thoracic and Cardio-Vascular Surgery , University Hospital of Rouen , Rouen , France.|b ABTE Toxemac, Rouen University , Rouen , France.
Arnaud
A
Gay
e Department of Pathology , University Hospital of Bordeaux , Bordeaux , France.
Hugues
H
Begueret
b ABTE Toxemac, Rouen University , Rouen , France.
Romain
R
Noël
b ABTE Toxemac, Rouen University , Rouen , France.
Jean-Paul
JP
Morin
a Department of Thoracic and Cardio-Vascular Surgery , University Hospital of Rouen , Rouen , France.|d INSERM, Rouen University , Rouen , France.
Pierre-Yves
PY
Litzler
D000241:Adenosine / Q000378:metabolism*; D056809:Alveolar Epithelial Cells / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003643:Death; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007376:Interleukin-2 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology*; D016040:Lung Transplantation; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D000241:Adenosine
adenosine; donation after cardiac death; inflammation; ischemia reperfusion; lung; transplant