Julia Scheiermann1, Dennis M Klinman1. 1. Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Abstract
BACKGROUND: Mechanical ventilation (MV) is commonly used to improve blood oxygenation in critically ill patients and for general anesthesia. Yet the cyclic mechanical stress induced at even moderate ventilation volume settings [tidal volume (Vt) <10 mL/kg] can injure the lungs and induce an inflammatory response. This work explores the effect of treatment with suppressive oligonucleotides (Sup ODN) in a mouse model of ventilator-induced lung injury (VILI). METHODS: Balb/cJ mice were mechanically ventilated for 4 h using clinically relevant Vt and a positive end-expiratory pressure of 3 cmH2O under 2-3% isoflurane anesthesia. Lung tissue and bronchoalveolar lavage fluid were collected to assess lung inflammation and lung function was monitored using a FlexiVent®. RESULTS: MV induced significant pulmonary inflammation characterized by the influx and activation of CD11c+/F4/80+ macrophages and CD11b+/Ly6G+ polymorphonuclear cells into the lung and bronchoalveolar lavage fluid. The concurrent administration of Sup ODN attenuated pulmonary inflammation as evidenced by reduced cellular influx and production of inflammatory cytokines. Oligonucleotide treatment did not worsen lung function as measured by static compliance or resistance. CONCLUSIONS: Treatment with Sup ODN reduces the lung injury induced by MV in mice.
BACKGROUND: Mechanical ventilation (MV) is commonly used to improve blood oxygenation in critically illpatients and for general anesthesia. Yet the cyclic mechanical stress induced at even moderate ventilation volume settings [tidal volume (Vt) <10 mL/kg] can injure the lungs and induce an inflammatory response. This work explores the effect of treatment with suppressive oligonucleotides (Sup ODN) in a mouse model of ventilator-induced lung injury (VILI). METHODS: Balb/cJ mice were mechanically ventilated for 4 h using clinically relevant Vt and a positive end-expiratory pressure of 3 cmH2O under 2-3% isoflurane anesthesia. Lung tissue and bronchoalveolar lavage fluid were collected to assess lung inflammation and lung function was monitored using a FlexiVent®. RESULTS: MV induced significant pulmonary inflammation characterized by the influx and activation of CD11c+/F4/80+ macrophages and CD11b+/Ly6G+ polymorphonuclear cells into the lung and bronchoalveolar lavage fluid. The concurrent administration of Sup ODN attenuated pulmonary inflammation as evidenced by reduced cellular influx and production of inflammatory cytokines. Oligonucleotide treatment did not worsen lung function as measured by static compliance or resistance. CONCLUSIONS: Treatment with Sup ODN reduces the lung injury induced by MV in mice.
Authors: Jesús Villar; Jesús Blanco; José Manuel Añón; Antonio Santos-Bouza; Lluís Blanch; Alfonso Ambrós; Francisco Gandía; Demetrio Carriedo; Fernando Mosteiro; Santiago Basaldúa; Rosa Lidia Fernández; Robert M Kacmarek Journal: Intensive Care Med Date: 2011-10-14 Impact factor: 17.440
Authors: Jesús Villar; Nuria Cabrera; Milena Casula; Carlos Flores; Francisco Valladares; Mercedes Muros; Lluis Blanch; Arthur S Slutsky; Robert M Kacmarek Journal: Intensive Care Med Date: 2010-04-16 Impact factor: 17.440
Authors: Esther K Wolthuis; Alexander P J Vlaar; Goda Choi; Joris J T H Roelofs; Nicole P Juffermans; Marcus J Schultz Journal: Crit Care Date: 2009-01-19 Impact factor: 9.097