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Effect of antibody-mediated connective tissue growth factor neutralization on lung edema in ventilator-induced lung injury in rats.
van den Brom, Charissa E; Bozic, Caitlin; Polet, Chantal A; Bongers, Annabel; Tuip-de Boer, Anita M; Ibelings, Roselique; Roelofs, Joris J T H; Juffermans, Nicole P.
Afiliación
  • van den Brom CE; Department of Anesthesiology, Amsterdam UMC, VU University, Amsterdam, The Netherlands. c.vandenbrom@amsterdamumc.nl.
  • Bozic C; Laboratory for Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. c.vandenbrom@amsterdamumc.nl.
  • Polet CA; Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. c.vandenbrom@amsterdamumc.nl.
  • Bongers A; Department of Anesthesiology, Amsterdam UMC, VU University, Amsterdam, The Netherlands.
  • Tuip-de Boer AM; Laboratory for Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Ibelings R; Laboratory for Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Roelofs JJTH; Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Juffermans NP; Laboratory for Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Mol Med ; 30(1): 68, 2024 May 22.
Article en En | MEDLINE | ID: mdl-38778274
ABSTRACT

BACKGROUND:

Acute respiratory distress syndrome (ARDS) is characterized by alveolar edema that can progress to septal fibrosis. Mechanical ventilation can augment lung injury, termed ventilator-induced lung injury (VILI). Connective tissue growth factor (CTGF), a mediator of fibrosis, is increased in ARDS patients. Blocking CTGF inhibits fibrosis and possibly vascular leakage. This study investigated whether neutralizing CTGF reduces pulmonary edema in VILI.

METHODS:

Following LPS administration, rats were mechanically ventilated for 6 h with low (6 mL/kg; low VT) or moderate (10 mL/kg; mod VT) tidal volume and treated with a neutralizing CTGF antibody (FG-3154) or placebo lgG (vehicle). Control rats without LPS were ventilated for 6 h with low VT. Lung wet-to-dry weight ratio, FITC-labeled dextran permeability, histopathology, and soluble RAGE were determined.

RESULTS:

VILI was characterized by reduced PaO2/FiO2 ratio (low VT 540 [381-661] vs. control 693 [620-754], p < 0.05), increased wet-to-dry weight ratio (low VT 4.8 [4.6-4.9] vs. control 4.5 [4.4-4.6], p < 0.05), pneumonia (low VT 30 [0-58] vs. control 0 [0-0]%, p < 0.05) and interstitial inflammation (low VT 2 [1-3] vs. control 1 [0-1], p < 0.05). FG-3154 did not affect wet-to-dry weight ratio (mod VT + FG-3154 4.8 [4.7-5.0] vs. mod VT + vehicle 4.8 [4.8-5.0], p > 0.99), extravasated dextrans (mod VT + FG-3154 0.06 [0.04-0.09] vs. mod VT + vehicle 0.04 [0.03-0.09] µg/mg tissue, p > 0.99), sRAGE (mod VT + FG-3154 1865 [1628-2252] vs. mod VT + vehicle 1885 [1695-2159] pg/mL, p > 0.99) or histopathology.

CONCLUSIONS:

'Double hit' VILI was characterized by inflammation, impaired oxygenation, pulmonary edema and histopathological lung injury. Blocking CTGF does not improve oxygenation nor reduce pulmonary edema in rats with VILI.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Edema Pulmonar / Lesión Pulmonar Inducida por Ventilación Mecánica / Factor de Crecimiento del Tejido Conjuntivo Límite: Animals Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Edema Pulmonar / Lesión Pulmonar Inducida por Ventilación Mecánica / Factor de Crecimiento del Tejido Conjuntivo Límite: Animals Idioma: En Revista: Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido