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Lung allografts are threatened by primary graft dysfunction, infections, and rejection. Novel therapies protecting pulmonary allografts are badly needed. Keratinocyte growth factor (KGF) protects the lung against a variety of injurious stimuli and exerts anti-inflammatory effects. The aim of the study was to test the potential of recombinant truncated KGF (ΔN23-KGF, palifermin) to attenuate pulmonary allograft rejection. Intratracheal instillation of 5 mg/kg ΔN23-KGF was performed twice in donor rats on days 3 and 2 before explantation of the lung. In control animals, an equivalent volume of vehicle was instilled. Left lungs were transplanted in the fully allogeneic Dark Agouti to Lewis rat strain combination and in the less stringent Fischer 344 to Wistar Kyoto combination. Allograft recipients were additionally treated with ΔN23-KGF post-transplantation. Graft outcome, leukocytic infiltration, and major histocompatibility complex (MHC) class II antigen expression was analyzed. In both rat strain combinations, ΔN23-KGF treatment did not improve pulmonary allograft outcome. Graft infiltration by macrophages and T lymphocytes remained unchanged. In addition, we demonstrated that MHC class II antigens were more abundant in KGF-treated allografts compared to control-treated grafts, which probably results in an increased alloreactivity. In conclusion, intratracheal ΔN23-KGF treatment is not effective to prevent acute pulmonary allograft rejection. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive assessment of experimental lung transplants with high resolution would be favorable to exclude technical failure and to follow up graft outcome in the living animal. Here we describe a flat-panel Volumetric Computed Tomography (fpVCT) technique using a prototype scanner. Methods: Lung transplantation was performed in allogeneic as well as in corresponding syngeneic rat strain combinations. At different time points post-transplantation, fpVCT was performed. Results: Lung transplants can be visualized in the living rat with high-spatial resolution. FpVCT allows a detailed analysis of the lung and the bronchi. Infiltrates developing during rejection episodes can be diagnosed and follow-up studies can easily be performed. Conclusions: With fpVCT it is possible to control the technical success of the surgical procedure. Graft rejection can be visualized individually in the living animal noninvasively, which is highly advantageous for studying the pathogenesis of chronic rejection or to monitor new therapies. [ABSTRACT FROM AUTHOR]

Background: Alterations to pulmonary surfactant composition have been encountered in the Acute Respiratory Distress Syndrome (ARDS). However, only few data are available regarding the time-course and duration of surfactant changes in ARDS patients, although this information may largely influence the optimum design of clinical trials addressing surfactant replacement therapy. We therefore examined the time-course of surfactant changes in 15 patients with direct ARDS (pneumonia, aspiration) over the first 8 days after onset of mechanical ventilation. Methods: Three consecutive bronchoalveolar lavages (BAL) were performed shortly after intubation (T0), and four days (T1) and eight days (T2) after intubation. Fifteen healthy volunteers served as controls. Phospholipid-to-protein ratio in BAL fluids, phospholipid class profiles, phosphatidylcholine (PC) molecular species, surfactant proteins (SP)-A, -B, -C, -D, and relative content and surface tension properties of large surfactant aggregates (LA) were assessed. Results: At T0, a severe and highly significant reduction in SP-A, SP-B and SP-C, the LA fraction, PC and phosphatidylglycerol (PG) percentages, and dipalmitoylation of PC (DPPC) was encountered. Surface activity of the LA fraction was greatly impaired. Over time, significant improvements were encountered especially in view of LA content, DPPC, PG and SP-A, but minimum surface tension of LA was not fully restored (15 mN/m at T2). A highly significant correlation was observed between PaO2/FiO2 and minimum surface tension (r = -0.83; p < 0.001), SP-C (r = 0.64; p < 0.001), and DPPC (r = 0.59; p = 0.003). Outcome analysis revealed that nonsurvivors had even more unfavourable surfactant properties as compared to survivors. Conclusion: We concluded that a profound impairment of pulmonary surfactant composition and function occurs in the very early stage of the disease and only gradually resolves over time. These observations may explain why former surfactant replacement studies with a short treatment duration failed to improve outcome and may help to establish optimal composition and duration of surfactant administration in future surfactant replacement studies in acute lung injury. [ABSTRACT FROM AUTHOR]