The online version of this article (doi:10.1186/1471-2253-14-42) contains supplementary material, which is available to authorized users.
All experiments were performed at the Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University, Mainz, Germany. The study was funded in part by APEPTICO, Vienna, Austria, which developed the peptides AP301 and AP318. APEPTICO had no influence on the performance of the experiments, data analysis and interpretation or manuscript drafting.
EKH coordinated and supervised the experiments. EKH, RT, TL, JS and AZ conducted the experiments. EKH, RT, BD and DE performed the data analysis. EKH drafted the manuscript. KM and MD participated in the study design, supervision of laboratory, data analysis and revision of the manuscript. All authors edited and approved the final manuscript.
Inhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two alternate peptide versions (TIP-A, TIP-B).
Following animal care committee approval ARDS was induced by bronchoalveolar lavage followed by injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group setting compared the single-dosed peptide variants TIP-A and TIP-B as well as single versus repetitive inhalation of TIP-A (n = 7 per group). Over two three-hour intervals parameters of gas exchange, transpulmonary thermodilution, calculated alveolar fluid clearance, and ventilation/perfusion-distribution were assessed. Post-mortem measurements included pulmonary wet/dry ratio and haemorrhage/congestion scoring.
The repetitive TIP-A inhalation led to a significantly lower wet/dry ratio than a single dose and a small but significantly lower EVLWI. However, EVLWI changes over time and the derived alveolar fluid clearance did not differ significantly. The comparison of TIP-A and B showed no relevant differences. Gas exchange and ventilation/perfusion-distribution significantly improved in all groups without intergroup differences. No differences were found in haemorrhage/congestion scoring.
In comparison to a single application the repetitive inhalation of a TIP peptide in three-hour intervals may lead to a small additional reduction the lung water content. Two alternate TIP peptide versions showed interchangeable characteristics.
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- TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants
Erik K Hartmann
- BioMed Central
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