23. Reduced Neutrophil Infiltration Protects Against Delayed Lung Reperfusion Injury Following Transplantation

Scott D. Ross, Curtis G. Tribble, John R. Gaughen, Jr., Kimberly S. Shockey, Patrick E. Parrino, Irving L. Kron

University of Virginia

Charlottesville, Va.

Discrepancies exist regarding the role of neutrophils in lung ischemia-reperfusion injury. We hypothesized that the late phase of reperfusion injury following transplantation is neutrophil dependent. Using our isolated, whole blood-perfused, ventilated rabbit lung model, we sought to define the pattern and mechanisms of delayed lung reperfusion injury after transplantation. Donor rabbits underwent lung harvest after pulmonary arterial PGE, injection and Euro-Collin preservation solution flush. Group I lungs (n=8) were immediately reperfused without ischemic storage. Group II lungs (n=8) were immediately reperfused without ischemic storage. Group II lungs (n=8) were stored for 18 hours at 4°C before perfusion. Group III lungs (n=10) underwent 18 hours of ischemic storage and were reperfused with whole blood that was first passed through a leukocyte-depleting filter. All lungs were reperfused for two hours, and pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and oxygenation were recorded. We measured Evans-blue dye (EBD) to determined microvascular permeability, myeloperoxidase (MPO) to quantify neutrophil sequestration and wet/dry weight ratios to demonstrate pulmonary edema.
 

 Group
Arterial pO2 (mmHg)
PAP (mmHg)
PVR (dynes.scm-5)
Wet/Dry Ratio
EBD 
(ng/g tissue)
MPO (ABS/g/min) 
I
188.03±45.31
38.31±2.36
43.822±3034
683±0.28^
89.29±5.07!
105.21±12.69
II
55.58±5.24
44.15±4.77
52.775±6386
8.79±0.41
117.16±12.78
102.84±10.41
III
272.58±58.97
27.85±1.45+
30,867±2323#
7.88±0.51
73.98±6.15!
56.92±6.31$
 *  p=0.001 v II     +  p=0.002 v all     #  p=0.003 v all     ^  p=0.019 v II     !  p=0.005 v II     $  p=0.002 v all

Leukocyte depletion of the blood reperfusate significantly improved oxygenation, PAP, and PVR, and had a significant protective effect against microvascular permeability. In addition, leukocyte depletion resulted in significantly reduced lung neutrophil sequestration, which suggests that the course of these neutrophils is the blood reperfusate. We conclude that the late phase of lung reperfusion injury is independent on both ischemia and neutrophil infiltration.

 
Program    1st Session    2nd Session    3rd Session    Th Forum    CV Forum    PGC
Revised October 9, 1998
STSA Web Editor