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

BMC Anesthesiol. 2014 May 26;14:42. doi: 10.1186/1471-2253-14-42. eCollection 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: ARDS; Alveolar fluid clearance; Lectin-like domain; Porcine model; Pulmonary oedema; TIP peptide.

Publication types

  • Comparative Study

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / pathology
  • Administration, Inhalation
  • Animals
  • Bronchoalveolar Lavage
  • Disease Models, Animal
  • Drug Administration Schedule
  • Extravascular Lung Water / drug effects*
  • Peptides / administration & dosage
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Pulmonary Gas Exchange
  • Swine
  • Thermodilution

Substances

  • Peptides
  • pepBs1-Ac peptide