title: Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs.
abstract: Mechanical ventilation (MV), using high tidal volumes (V(T)), causes lung (ventilator-induced lung injury [VILI]) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. Protein carbonylation and nitration, antioxidants, and inflammation (immunoblotting) were evaluated in diaphragm, gastrocnemius, soleus, myocardium, and lungs of nonseptic and septic (cecal ligation and puncture 24 hours before MV) rats undergoing MV (n = 7 per group) for 150 minutes using 3 different strategies (low V(T) [V(T) = 9 mL/kg], moderate V(T) [V(T) = 15 mL/kg], and high V(T) [V(T) = 25 mL/kg]) and in nonventilated control animals. Compared with nonventilated control animals, in septic and nonseptic rodents (1) diaphragms, limb muscles, and myocardium of high-V(T) rats exhibited a decrease in protein oxidation and nitration levels, (2) antioxidant levels followed a specific fiber-type distribution in slow- and fast-twitch muscles, (3) tumor necrosis factor α (TNF-α) levels were higher in respiratory and limb muscles, whereas no differences were observed in myocardium, and (4) in lungs, protein oxidation was increased, antioxidants were rather decreased, and TNF-α remained unmodified. In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V(T), whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents.
authors.affiliation: Pulmonology Department-Muscle and Respiratory System Research Unit, Institut Municipal d'Investigació Mèdica (IMIM)-Hospital del Mar, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain; Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra, PRBB, Barcelona, Spain; Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Chacon-Cabrera
authors.affiliation: Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Intensiva, Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Getafe, Madrid, Spain.
authors.forename: Yeny
authors.initials: Y
authors.lastname: Rojas
authors.affiliation: Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Intensiva, Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Getafe, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Martínez-Caro
authors.affiliation: Pulmonology Department-Muscle and Respiratory System Research Unit, Institut Municipal d'Investigació Mèdica (IMIM)-Hospital del Mar, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain; Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra, PRBB, Barcelona, Spain; Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Vila-Ubach
authors.affiliation: Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Intensiva, Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Getafe, Madrid, Spain; Servicio de Medicina Intensiva, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nin
authors.affiliation: Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Intensiva, Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Getafe, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferruelo
authors.affiliation: Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Intensiva, Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Getafe, Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Esteban
authors.affiliation: Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Servicio de Medicina Intensiva, Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Getafe, Madrid, Spain; Universidad Europea de Madrid, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.affiliation: Pulmonology Department-Muscle and Respiratory System Research Unit, Institut Municipal d'Investigació Mèdica (IMIM)-Hospital del Mar, Parc de Recerca Biomèdica de Barcelona (PRBB), Barcelona, Spain; Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra, PRBB, Barcelona, Spain; Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Electronic address: ebarreiro@imim.es.
authors.forename: Esther
authors.initials: E
authors.lastname: Barreiro
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003964:Diaphragm / Q000378:metabolism / Q000473:pathology*; D005121:Extremities / Q000473:pathology*; D006439:Hemodynamics; D015151:Immunoblotting; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers