PATTERN OF INJURY AND THE ROLE OF NEUTROPHILS IN REPERFUSION INJURY OF RAT LUNG

Using a rat lung model, we sought to characterize the time course for ischemia-reperfusion injury and the role of neutrophils in the develop ment of injury, Adult male Long-Evans rats underwent left thoracotomy with dissection and clamping of the left pulmonary artery, bronchus, a nd vein for 90 min, resulting in complete left lung ischemia, The lung s were then ventilated and reperfused for up to 4 hr, Time-matched sha m animals underwent the identical thoracotomy and hilar dissection, bu t the lungs were not rendered ischemic, Using vascular permeability of I-125-labeled bovine serum albumin as a measure of reperfusion injury , a bimodal pattern of injury was observed, Compared to sham controls, animals undergoing ischemia-reperfusion demonstrated a significant ea rly phase of lung injury at 30 min of reperfusion (P < 0.0001), follow ed by partial recovery, A second peak of lung injury was noted after 4 hr of reperfusion (P < 0.001), Myeloperoxidase activity in reperfused lung tissue, a measure of neutrophil sequestration, increased during the reperfusion time course, To determine the role of neutrophils in t he development of lung reperfusion injury, additional animals undergoi ng the identical ischemia-reperfusion protocol received either rabbit anti-rat neutrophil serum or preimmune serum the day prior to operatio n, Profound neutropenia (<75/mm(3) blood) was confirmed by differentia l leukocyte counts, Neutropenia had no protective effect against micro vascular permeability at 30 min of reperfusion, but there was a signif icant reduction in lung injury at 4 hr (P < 0.005), We conclude that, during lung ischemia-reperfusion, there is a bimodal pattern of injury , consisting of both neutrophil-independent and neutrophil-mediated ev ents. (C) 1995 Academic Press, Inc.