Lung injury after in vivo reperfusion: outcome at 27 hours after reperfusion.
BACKGROUND
Although short-term findings after lung reperfusion have been extensively reported, in vivo animal studies have not described outcome beyond the immediate time period. Therefore, the authors evaluated lung injury 27 h after reperfusion. They also investigated whether attenuation of lung injury with the A3 adenosine receptor agonist MRS3558 was sustained beyond the immediate time period.


METHODS
In intact-chest, spontaneously breathing cats in which the left lower lung lobe was isolated and subjected to 2 h of ischemia and 3 h of reperfusion, MRS3558 was administered before reperfusion. Animals were killed 3 or 27 h after reperfusion.


RESULTS
When compared with 3 h of reperfusion, at 27 h the left lower lobe showed reduced apoptosis and no change in inflammation, but increased edema. Increased edema of the nonischemic right lung and hypoxemia were observed at 27 h after left lower lobe reperfusion. Increases in phosphorylated p38 levels were found at 3 h of reperfusion compared with control lung, with further increases at 27 h. The attenuation of injury observed with MRS3558 treatment at 3 h of reperfusion was sustained at 27 h.


CONCLUSIONS
Lung edema may worsen hours after the immediate postreperfusion period, even though lung apoptosis and inflammation are reduced or show no change, respectively. This was associated with further increases in phosphorylated p38 levels. The nonischemic lung may also be affected, suggesting a systemic response to reperfusion. In addition, early attenuation of injury is beneficial beyond the immediate period after reperfusion. Treatment aimed at inhibiting p38 activation, such as A3 receptor activation, should be further studied to explore its potential long-term beneficial effect.
Matot
Idit
I
Department of Anesthesiology and Critical Care Medicine, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. iditm@tasmc.health.gov.il
Einav
Sharon
S
Weiniger
Carolyn F
CF
Pearl
Ron G
RG
Abramovitch
Rinat
R
Joshi
Balachandra V
BV
Jacobson
Kenneth A
KA
D058909:Adenosine A3 Receptor Agonists; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001784:Blood Gas Analysis; D002415:Cats; D008171:Lung Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000378:metabolism
D058909:Adenosine A3 Receptor Agonists; D048069:Tumor Necrosis Factors; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases