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Hypercapnic Acidosis Attenuates Endotoxin-induced Acute Lung Injury

Department of Physiology, Conway Institute of Biomolecular and Biomedical Research and Dublin Molecular Medicine Centre, University College Dublin; and Department of Anaesthesia, Intensive Care and Pain Medicine, St Vincent's University Hospital, Dublin, Ireland

Correspondence and requests for reprints should be addressed to John Laffey, M.D., Department of Physiology, University College Dublin, Earlsfort Terrace, Dublin 2, Ireland. E-mail: j.laffey{at}ireland.com

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.

Key Words: acute respiratory distress syndrome • hypercapnic acidosis • nitric oxide • rat • sepsis

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