Authors:	Hartmann, Erik Thomas, Rainer Liu, Tanghua Stefaniak, Joanna Ziebart, Alexander Duenges, Bastian Eckle, Daniel Markstaller, Klaus David, Matthias
Title:	TIP peptide inhalation in experimental acute lung injury : effect of repetitive dosage and different synthetic variants
Online publication date:	15-Jun-2022
Year of first publication:	2014
Language:	english
Abstract:	BACKGROUND: Inhalation of TIP peptides that mimic the lectin-like domain of TNF-alpha 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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7157
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	http://creativecommons.org/licenses/by/2.0/
Journal:	BMC anesthesiology 14
Pages or article number:	Art. 42
Publisher:	BioMed central
Publisher place:	S.l.
Issue date:	2014
ISSN:	1471-2253
Publisher URL:	http://dx.doi.org/10.1186/1471-2253-14-42
Publisher DOI:	10.1186/1471-2253-14-42
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)