An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was associated with an increase in alveolar surfactant components. Left lungs with 6-h (n = 8) or prolonged 20-h ischemia (n = 10) were transplanted syngeneically in rats. In both ischemia groups half of the lung transplants were treated with surfactant just before reperfusion. Lung function was measured during reperfusion for 1 h. Thereafter, the rats were killed and bronchoalveolar lavage was performed to measure alveolar surfactant components. We found that surfactant treatment improved the immediate function of lung transplants in parallel with a higher amount of total surfactant phospholipids, a higher percentage of the heavy subtype of surfactant, a normalized percentage of phosphatidylcholine, and a higher amount of endogenous surfactant protein A (SP-A). We conclude that surfactant treatment before reperfusion does improve the immediate lung transplant function in rats in association with an increase in alveolar surfactant components. More particularly, the amount of (endogenous) SP-A is thought to be crucial for the efficacy of surfactant treatment after lung transplantation.

This study shows that brain death induces an inflammatory response in the donor lung and subsequently aggravates chronic rejection after transplantation. This may explain the clinical difference in long-term function between lungs from cadaveric donors and living donors.

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The lung is a common target in systemic vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA). In the present study, we tested the hypothesis that the presence of antibodies directed against myeloperoxidase (MPO) induces pulmonary (vasculitic) lesions when neutrophils release lysosomal enzymes. Brown Norway (BN) rats were immunized with human MPO in complete Freund's adjuvant (CFA) or with CFA alone. Two weeks after immunization, rats had developed antibodies to human and rat MPO. Next, isolated single left lung perfusion was performed with human neutrophil lysosomal extract containing MPO and proteolytic enzymes. Rats were killed at 15 min, 4 h, and 10 d after perfusion. Tissue samples from the left and right lung were examined for vasculitic lesions and inflammatory cell infiltrates. At 15 min and 4 h, left lungs from control and MPO-immunized rats showed a mild influx of polymorphonuclear cells. At 10 d, patchy inflammatory cell infiltrates, consisting predominantly of polymorphonuclear leukocytes (PMNs) and monocytes, were observed throughout the parenchyma of the left lung in MPO-immunized rats. Occasionally, granuloma-like lesions, giant cells, and foci of alveolar hemorrhage were observed as well. Far less severe lesions were seen in control immunized rats. Strikingly, at 10 d after perfusion, severe pulmonary tissue injury was observed also in right lungs from MPO-immunized rats whereas right lungs from control immunized rats appeared normal. The lesions were characterized by influx of PMNs and monocytes and, in some rats, foci of alveolar hemorrhage. These studies suggest that the presence of an anti-MPO directed autoimmune response contributes to generalized pulmonary tissue injury after local release of products of activated neutrophils, which supports a pathogenic role of MPO-ANCA.