OBJECTIVE: Acute respiratory distress syndrome is occasionally seen in newborn infants due to a severe inflammatory process in the lungs that affects capillary-alveolar permeability, epithelial integrity, and type I and II pneumocyte function. The aim of this study was to investigate the effect of a topically applied nuclear factor-kappaB inhibitor (IkappaB kinase-NF-kappaB essential modulator binding domain [IKK-NBD] peptide) on gas exchange, lung function, lung fluids, and inflammation in a piglet model of repeated airway lavage that is characterized by surfactant deficiency, lung edema, and an inflammatory response. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory of a university children's hospital. SUBJECTS: A total of 24 anesthetized, mechanically ventilated newborn piglets. INTERVENTIONS: Repeated airway lavage was carried out until both the Pao2 decreased to approximately 40 mm Hg, while ventilating the piglets with an Fio2 of 0.6, and a peak inspiratory pressure of >/=18 cm H2O was needed to maintain tidal volume at 6 mL/kg. One group of piglets served as a control (n = 8), a second group (S, n = 8) received a porcine surfactant preparation (Curosurf), and a third group received IKK-NBD peptide admixed to surfactant (S+IN, n = 8). MEASUREMENTS AND MAIN RESULTS: After 6 hrs of mechanical ventilation after intervention, S+IN group piglets showed decreased extravascular lung water (S+IN vs. S, 20 +/- 3 vs. 28 +/- 10 mL/kg; p < .05) and a lesser protein content in the epithelial lining fluid (S+IN vs. S, 38 +/- 5 vs. 50 +/- 5 mg/L; p < .05). Functional residual capacity (S+IN vs. S, 16.7 +/- 6.3 vs. 12.2 +/- 4.3 mL/kg; p < .05), alveolar volume (S+IN vs. S, 5.4 +/- 1.8 vs. 4.6 +/- 1.5 mL/kg; p < .05), and lung mechanics were improved. Bronchoalveolar lavage showed a lesser percentage of polymorphonuclear leukocytes (S+IN vs. S, 70% +/- 6% vs. 82% +/- 3%; p < .01) and a reduction in the chemokine leukotriene B4 (S+IN vs. S, 2.0 +/- 0.6 vs. 3.5 +/- 1.4 pg/mL; p < .01). CONCLUSIONS: A topically applied nuclear factor-kappaB inhibitor improves lung edema and lung volumes and reduces inflammation in this newborn piglet model of airway lavage.
OBJECTIVE: Acute respiratory distress syndrome is occasionally seen in newborn infants due to a severe inflammatory process in the lungs that affects capillary-alveolar permeability, epithelial integrity, and type I and II pneumocyte function. The aim of this study was to investigate the effect of a topically applied nuclear factor-kappaB inhibitor (IkappaB kinase-NF-kappaB essential modulator binding domain [IKK-NBD] peptide) on gas exchange, lung function, lung fluids, and inflammation in a piglet model of repeated airway lavage that is characterized by surfactant deficiency, lung edema, and an inflammatory response. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory of a university children's hospital. SUBJECTS: A total of 24 anesthetized, mechanically ventilated newborn piglets. INTERVENTIONS: Repeated airway lavage was carried out until both the Pao2 decreased to approximately 40 mm Hg, while ventilating the piglets with an Fio2 of 0.6, and a peak inspiratory pressure of >/=18 cm H2O was needed to maintain tidal volume at 6 mL/kg. One group of piglets served as a control (n = 8), a second group (S, n = 8) received a porcine surfactant preparation (Curosurf), and a third group received IKK-NBD peptide admixed to surfactant (S+IN, n = 8). MEASUREMENTS AND MAIN RESULTS: After 6 hrs of mechanical ventilation after intervention, S+IN group piglets showed decreased extravascular lung water (S+IN vs. S, 20 +/- 3 vs. 28 +/- 10 mL/kg; p < .05) and a lesser protein content in the epithelial lining fluid (S+IN vs. S, 38 +/- 5 vs. 50 +/- 5 mg/L; p < .05). Functional residual capacity (S+IN vs. S, 16.7 +/- 6.3 vs. 12.2 +/- 4.3 mL/kg; p < .05), alveolar volume (S+IN vs. S, 5.4 +/- 1.8 vs. 4.6 +/- 1.5 mL/kg; p < .05), and lung mechanics were improved. Bronchoalveolar lavage showed a lesser percentage of polymorphonuclear leukocytes (S+IN vs. S, 70% +/- 6% vs. 82% +/- 3%; p < .01) and a reduction in the chemokine leukotriene B4 (S+IN vs. S, 2.0 +/- 0.6 vs. 3.5 +/- 1.4 pg/mL; p < .01). CONCLUSIONS: A topically applied nuclear factor-kappaB inhibitor improves lung edema and lung volumes and reduces inflammation in this newborn piglet model of airway lavage.
Authors: Anita Gaurnier-Hausser; Reema Patel; Albert S Baldwin; Michael J May; Nicola J Mason Journal: Clin Cancer Res Date: 2011-05-24 Impact factor: 12.531
Authors: Jing Zhao; Lei Zhang; Xiaodong Mu; Christelle Doebelin; William Nguyen; Callen Wallace; Daniel P Reay; Sara J McGowan; Lana Corbo; Paula R Clemens; Gabriela Mustata Wilson; Simon C Watkins; Laura A Solt; Michael D Cameron; Johnny Huard; Laura J Niedernhofer; Theodore M Kamenecka; Paul D Robbins Journal: PLoS Biol Date: 2018-06-11 Impact factor: 8.029