title: TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants.
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.
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Hartmann
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Tanghua
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Anaesthesiology, General Critical Care Medicine and Pain Therapy, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Joanna
authors.initials: J
authors.lastname: Stefaniak
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ziebart
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Duenges
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eckle
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany ; Department of Anaesthesiology, General Critical Care Medicine and Pain Therapy, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Markstaller
authors.affiliation: Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: David
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D015633:Extravascular Lung Water / Q000187:drug effects*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange; D013552:Swine; D013815:Thermodilution
chemical_list: D010455:Peptides; C521715:pepBs1-Ac peptide
keywords: ARDS; Alveolar fluid clearance; Lectin-like domain; Porcine model; Pulmonary oedema; TIP peptide