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: Erik K Hartmann, Rainer Thomas, Tanghua Liu, Joanna Stefaniak, Alexander Ziebart, Bastian Duenges, Daniel Eckle, Klaus Markstaller, Matthias David
• Journal: BMC anesthesiology (BMC Anesthesiol) Vol. 14 Pg. 42 ( 2014) ISSN: 1471-2253 [Print] England
• PMID: 24904234 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Peptides
• pepBs1-Ac peptide

Topics

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