title: Complement activation contributes to ventilator-induced lung injury in rats.
abstract: The complement system contributes to ventilator induced lung injury (VILI). We hypothesized that pretreatment with the C1 esterase inhibitor (C1INH) Berinert® constrains complement activation consecutively inducing improvements in arterial oxygenation and histological pulmonary damage. At baseline, male Sprague-Dawley rats underwent mechanical ventilation in a conventional mode (PIP 13 cm H2O, PEEP 3 cm H2O). In the Control group, the ventilator setting was maintained (Control, n = 15). The other animals randomly received intravenous pretreatment with either 100 units/kg of the C1-INH Berinert® (VILI-C1INH group, n = 15) or 1 ml saline solution (VILI-C group, n = 15). VILI was induced by invasive ventilation (PIP 35 cm H2O, PEEP 0 cm H2O). After two hours of mechanical ventilation, the complement component C3a remained low in the Control group (258 ± 82 ng/ml) but increased in both VILI groups (VILI-C: 1017 ± 283 ng/ml; VILIC1INH: 817 ± 293 ng/ml; P < 0.05 for both VILI groups versus Control). VILI caused a profound deterioration of arterial oxygen tension (VILI-C: 193 ± 167 mmHg; VILI/C1-INH: 154 ± 115 mmHg), whereas arterial oxygen tension remained unaltered in the Control group (569 ± 26 mmHg; P < 0.05 versus both VILI groups). Histological investigation revealed prominent overdistension and interstitial edema in both VILI groups compared to the Control group. C3a plasma level in the VILI group were inversely correlated with arterial oxygen tension (R = -0.734; P < 0.001). We conclude that in our animal model of VILI the complement system was activated in parallel with the impairment in arterial oxygenation and that pretreatment with 100 units/kg Berinert® did neither prevent systemic complement activation nor lung injury.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Faculty, Leipzig, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Petersen
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Faculty, Leipzig, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Busch
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Schoen Clinics, Vogtareuth, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Gaertner
authors.affiliation: Department of Anesthesiology, Erasmus University Medical Center, Rotterdam, The Netherland.|Departments of Anesthesiology and Intensive Care, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Haitsma
authors.affiliation: Department of Anesthesiology, Erasmus University Medical Center, Rotterdam, The Netherland.
authors.forename: S
authors.initials: S
authors.lastname: Krabbendam
authors.affiliation: Institute of Pathology, Community Hospital, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ebsen
authors.affiliation: Department of Anesthesiology, Erasmus University Medical Center, Rotterdam, The Netherland.|Department of Anesthesiology and Intensive Care, Charite University Medical Center, Campus Virchow Klinikum and Campus Charite-Mitte, Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Lachmann
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Faculty, Leipzig, Germany.|University Hospital, Ulm, Germany. Udo.Kaisers@uniklinik-ulm.de.
authors.forename: U X
authors.initials: UX
authors.lastname: Kaisers
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D050718:Complement C1 Inhibitor Protein / Q000494:pharmacology; D015926:Complement C3a / Q000276:immunology; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology*; D008297:Male; D010100:Oxygen / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000379:methods; D055397:Ventilator-Induced Lung Injury / Q000276:immunology*
chemical_list: D050718:Complement C1 Inhibitor Protein; D015926:Complement C3a; D010100:Oxygen