Introduction:The lectin‐like domain of TNF‐α enhances the fluid clearance across the alveolar barrier. For experimental purposes, the lectin‐like domain can be mimicked by a synthetic peptide representing the TIP‐motif of TNF‐α. The present study aims to assess the acute effect of TIP on the pulmonary function in a porcine model of acute respiratory distress syndrome (ARDS).
Methods:Lung injury was induced in 16 pigs (25–27 kg) by bronchoalveolar lavage followed by injurious ventilation. Following randomisation, either nebulised TIP (1 mg/kg; AP301, APEPTICO, Vienna, Austria) or water for injection (control group) was administered. During 5 h of monitoring, the extravascular lung water index (EVLWI), the quotient of partial pressure of oxygen and inspired oxygen concentration (PaO2/FiO2) and the pulmonary shunt fraction were repetitively assessed. The data were evaluated by an analysis of variance including Bonferroni–Holm correction.
Results:Comparable baseline conditions in both groups were achieved. Ventilatory parameters were standardised in both groups. In the TIP group, a significant reduction of the EVLWI and a simultaneous increase in the PaO2/FiO2 ratio was shown (each P < 0.0001). No changes in the control group were observed (EVLWI: P = 0.43, PaO2/FiO2: P = 0.60). The intergroup comparison demonstrates a significant advantage of TIP inhalation over placebo (EVLWI: P < 0.0001, PaO2/FiO2: P = 0.004, shunt fraction: P = 0.0005).
Conclusions:The inhalation of TIP induces an amelioration of clinical surrogate parameters of the lung function in a porcine lung injury model. By mimicking the lectin‐like domain, the synthetic TIP peptide AP301 is an innovative approach as supportive therapy in ARDS.
