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Open Access Research article

TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants

Erik K Hartmann1*, Rainer Thomas1, Tanghua Liu1, Joanna Stefaniak2, Alexander Ziebart1, Bastian Duenges1, Daniel Eckle1, Klaus Markstaller12 and Matthias David1

Author Affiliations

1 Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany

2 Department of Anaesthesiology, General Critical Care Medicine and Pain Therapy, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria

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BMC Anesthesiology 2014, 14:42  doi:10.1186/1471-2253-14-42

Published: 26 May 2014

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.

Keywords:
TIP peptide; Lectin-like domain; Pulmonary oedema; Alveolar fluid clearance; ARDS; Porcine model