Premium
An inhaled tumor necrosis factor‐alpha‐derived TIP peptide improves the pulmonary function in experimental lung injury
Author(s) -
HARTMANN E. K.,
BOEHME S.,
DUENGES B.,
BENTLEY A.,
KLEIN K. U.,
KWIECIEN R.,
SHI C.,
SZCZYRBA M.,
DAVID M.,
MARKSTALLER K.
Publication year - 2013
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.12034
Subject(s) - medicine , ards , pulmonary shunt , anesthesia , bronchoalveolar lavage , fraction of inspired oxygen , lung , inhalation , mechanical ventilation
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; AP 301, APEPTICO , V ienna, A ustria) 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 ( PaO 2 / FiO 2 ) and the pulmonary shunt fraction were repetitively assessed. The data were evaluated by an analysis of variance including B onferroni– H olm 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 PaO 2 / FiO 2 ratio was shown (each P < 0.0001). No changes in the control group were observed ( EVLWI : P = 0.43, PaO 2 / FiO 2 : P = 0.60). The intergroup comparison demonstrates a significant advantage of TIP inhalation over placebo ( EVLWI : P < 0.0001, PaO 2 / FiO 2 : 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 AP 301 is an innovative approach as supportive therapy in ARDS .