Abstract:IntroductionThe objectives were to characterize alveolar fluid clearance (AFC) in pigs with normal lungs and to analyze the effect of immediate application of positive end-expiratory pressure (PEEP).MethodsAnimals (n = 25) were mechanically ventilated and divided into four groups: small edema (SE) group, producing pulmonary edema (PE) by intratracheal instillation of 4 ml/kg of saline solution; small edema with PEEP (SE + PEEP) group, same as previous but applying PEEP of 10 cmH2O; large edema (LE) group, prod… Show more
“…Using transpulmonary thermodilution in pigs, Garcia-Delgado et al (21) found a slightly higher rate of decrease in EVLWI under levels of positive end-expiratory pressure similar to the ones we used. Using transpulmonary thermodilution in pigs, Garcia-Delgado et al (21) found a slightly higher rate of decrease in EVLWI under levels of positive end-expiratory pressure similar to the ones we used.…”
“…Using transpulmonary thermodilution in pigs, Garcia-Delgado et al (21) found a slightly higher rate of decrease in EVLWI under levels of positive end-expiratory pressure similar to the ones we used. Using transpulmonary thermodilution in pigs, Garcia-Delgado et al (21) found a slightly higher rate of decrease in EVLWI under levels of positive end-expiratory pressure similar to the ones we used.…”
“…Patients suffering from a high-grade AFC impairment in early ARDS have significantly higher mortality rates [4]. The present model implies a sustained effect of the TIP peptide on the initial alveolar flooding, which, in the absence of recruitment or PEEP [18], is consistent with a resolution of oedema fluid. Hence, an early enhancement of the alveolar fluid clearance may not only reduce the lung water content but also lead to more homogenous lung tissue.…”
BackgroundInhalation 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).MethodsFollowing 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.ResultsThe 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.ConclusionsIn 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.
“…Mechanical ventilation and the applied PEEP are also presumed to play an important role in pulmonary edema formation, but the empirical results are conflicting. Some studies show that the application of high PEEP causes more pulmonary edema formation and lung damage [27][28][29], whereas others show that higher PEEP results in less pulmonary edema by increasing alveolar fluid clearance [30]. These conflicting results reflect the complexity of the mechanisms underlying pulmonary edema formation.…”
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