Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets.

Autor: Audard J; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France.; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Godet T; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France.; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Blondonnet R; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France.; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Joffredo JB; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France.; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Paquette B; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France.; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Belville C; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Lavergne M; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Gross C; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Pasteur J; Department of Dermatology, CHU Clermont-Ferrand, Clermont, Ferrand, France., Bouvier D; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France.; Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, Clermont, Ferrand, France., Blanchon L; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Sapin V; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France.; Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, Clermont, Ferrand, France., Pereira B; Biostatistical and Data Management Unit, Department of Clinical Research and Innovation (DRCI), CHU Clermont-Ferrand, Clermont, Ferrand, France., Constantin JM; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France.; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France., Jabaudon M; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France. mjabaudon@chu-clermontferrand.fr.; Université Clermont Auvergne, CNRS UMR 6293, INSERM U1103, GReD, Clermont, Ferrand, France. mjabaudon@chu-clermontferrand.fr.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Jun 25; Vol. 9 (1), pp. 9227. Date of Electronic Publication: 2019 Jun 25.
DOI: 10.1038/s41598-019-45798-5
Abstrakt: The receptor for advanced glycation end-products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will require assessment of this strategy in larger animals. Forty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid (i) alone; (ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), or (iii) recombinant soluble (s)RAGE. The primary outcome was net AFC at 4 h. Arterial oxygenation was assessed hourly and alveolar-capillary permeability, alveolar inflammation and lung histology were assessed at 4 h. Treatment with either RAP or sRAGE improved net AFC (median [interquartile range], 21.2 [18.8-21.7] and 19.5 [17.1-21.5] %/h, respectively, versus 12.6 [3.2-18.8] %/h in injured, untreated controls), oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after ARDS. These findings suggest that RAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.
Databáze: MEDLINE
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