Article
Inhalative application of synthetic cyclic peptide AP301 improves lung function during ex vivo lung perfusion
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Published: | October 14, 2013 |
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Objective: Ex vivo lung perfusion (EVLP) has emerged as a new technique to evaluate and improve marginal donor lungs prior to transplantation. The synthetic cyclic peptide AP301 has been shown to reduce oedema formation and neutrophile count in the air space in acute lung injury. We sought to investigate the impact of inhalative application of AP301 during EVLP of severely predamaged donor lungs in a porcine model.
Methods: Brain death was induced in donor animals by intracranial balloon inflation. The lungs were retrieved after 4 hours and subjected to 24 hours of cold ischemic time. Thereafter normothermic EVLP was performed for 4 hours in standard mode in 9 pigs (group 1) and with additional inhalative application of 1mg/kg nebulized AP301 at the beginning of ventilation in 9 pigs (group 2). Ventilation was started 30 minutes after initiation of EVLP at normothermia. Arterio-venous Po2 difference (delta pO2), compliance, peak airway pressures, pulmonary artery pressure were assessed at 1, 2, 3 and 4 hours of EVLP.
Results: Both groups were comparable in baseline values. Compliance was 19.7 ml/mbar vs. 33.2 ml/mbar (group 1 vs. group 2, p=0.03) at 1 hours of EVLP, 20.3 ml/mbar vs 31.3 ml/mbar at 2 hours p=0.06, n.s., 18.4 ml/mbar vs. 27.2 ml/mbar at 3 hours p=0.14, n.s. and 16.1 ml/mbar vs 25.7 ml/mbar at 4 hours (p=0.97, n.s.). Peak airway pressures and pulmonary artery pressures were comparable in both groups at all measurements as well. There was a trend towards improved delta pO2 in group 2 after 1 hour (116 mmHg vs. 137 mmHg, p=0.76, n.s.) and during the entire duration of EVLP (285 mmHg vs. 377 mmHg at 2 hours, 252 mmHg vs. 365 mmHg at 3 hours and 303 mmHg vs. 364 mmHg at 4 hours, all p=n.s). See Table 1 [Tab. 1].
Conclusion: Inhalative application of nebulized AP301 during EVLP of severely predamaged donor lungs provides a trend towards improved lung function compared to standard EVLP in a porcine model. Reconditioning of impaired donor lungs with EVLP and AP301 might help to increase the number of available donor lungs.