title: Hypercapnic acidosis attenuates endotoxin-induced acute lung injury.
abstract: Deliberate induction of prophylactic hypercapnic acidosis protects against lung injury after in vivo ischemia-reperfusion and ventilation-induced lung injury. However, the efficacy of hypercapnic acidosis in sepsis, the commonest cause of clinical acute respiratory distress syndrome, is not known. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would be protective against endotoxin-induced lung injury in an in vivo rat model. Prophylactic institution of hypercapnic acidosis (i.e., induction before endotoxin instillation) attenuated the decrement in arterial oxygenation, improved lung compliance, and attenuated alveolar neutrophil infiltration compared with control conditions. Therapeutic institution of hypercapnic acidosis, that is, induction after endotoxin instillation, attenuated the decrement in oxygenation, improved lung compliance, and reduced alveolar neutrophil infiltration and histologic indices of lung injury. Therapeutic hypercapnic acidosis attenuated the endotoxin-induced increase in the higher oxides of nitrogen and nitrosothiols in the lung tissue and epithelial lining fluid. Lung epithelial lining fluid nitrotyrosine concentrations were increased with hypercapnic acidosis. We conclude that hypercapnic acidosis attenuates acute endotoxin-induced lung injury, and is efficacious both prophylactically and therapeutically. The beneficial actions of hypercapnic acidosis were not mediated by inhibition of peroxynitrite-induced nitration within proteins.
authors.affiliation: Department of Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. j.laffey@ireland.com
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
authors.forename: Dave
authors.initials: D
authors.lastname: Honan
authors.forename: Natalie
authors.initials: N
authors.lastname: Hopkins
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Hyvelin
authors.forename: John F
authors.initials: JF
authors.lastname: Boylan
authors.forename: Paul
authors.initials: P
authors.lastname: McLoughlin
mesh_terms: D000142:Acidosis, Respiratory / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004731:Endotoxins; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D011322:Primary Prevention / Q000379:methods; D011336:Probability; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012131:Respiratory Insufficiency / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D004731:Endotoxins