Reduced neutrophil infiltration protects against lung reperfusion injury after transplantation.
BACKGROUND
There is evidence that lung ischemia reperfusion injury is a result of the activation of components of the inflammatory cascade. However, the role of neutrophils in lung reperfusion injury continues to be a source of controversy.


METHODS
Using an isolated, whole blood-perfused, ventilated rabbit lung model, we sought to characterize the pattern of reperfusion injury and investigate the contribution of neutrophils to this injury. Donor rabbits underwent lung harvest after pulmonary arterial prostaglandin E1 injection and Euro-Collins preservation solution flush. Group I lungs (n = 8) were immediately reperfused without ischemic storage. Group II lungs (n = 8) were stored for 18 h at 4 degrees C before reperfusion. Group III lungs (n = 10) underwent 18 h of ischemic storage and were reperfused with whole blood that was first passed through a leukocyte-depleting filter. All lungs were reperfused for 2 h.


RESULTS
Arterial oxygenation in group III progressively improved, and was significantly higher than that of group II after 2 h of reperfusion (272.58+/-58.97 vs 53.58+/-5.34 mm Hg, p = 0.01). Both pulmonary artery pressure and pulmonary vascular resistance were significantly reduced in group III when compared with group II (27.85+/-1.45 vs 44.15+/-4.77 mm Hg, p = 0.002; and 30,867+/-2,323 vs 52,775+/-6,386 dynes x sec x cm(-5), p = 0.003, respectively). Microvascular permeability in group III lungs was reduced to 73.98+/-6.15 compared with 117.16+/-12.78 ng Evans blue dye/g tissue in group II (p = 0.005). Group III myeloperoxidase activity was 56.92+/-6.31 deltaOD/g/min compared with 102.84+/-10.41 delta0d/g/min in group II (p = 0.002).


CONCLUSIONS
Leukocyte depletion of the blood reperfusate protects against microvascular permeability and significantly improves pulmonary graft function. The neutrophil plays a major role in amplifying lung injury later during reperfusion, and this lung ischemia reperfusion injury may be reversed through the interruption of the inflammatory cascade and the interference with neutrophil infiltration.
Ross
S D
SD
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Tribble
C G
CG
Gaughen
J R
JR
Shockey
K S
KS
Parrino
P E
PE
Kron
I L
IL
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D016040:Lung Transplantation; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control*; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*
D009195:Peroxidase