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Hypercapnic acidosis attenuates severe acute bacterial pneumonia-induced lung injury by a neutrophil-independent mechanism*

Ni Chonghaile, Martina MB, FCARCSI; Higgins, Brendan D. PhD; Costello, Joseph F. MB, FCARCSI; Laffey, John G. MD, FFARCSI

doi: 10.1097/CCM.0b013e31818f0d13
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Objective: Deliberate induction of hypercapnic acidosis protects against lung injury after nonseptic lung injury. In contrast, concerns exist regarding the effects of hypercapnic acidosis in the setting of severe pulmonary sepsis. The potential for the effects of hypercapnic acidosis to be neutrophil-mediated remains to be determined. We investigated whether hypercapnic acidosis—induced by adding CO2 to inspired gas—would protect against severe acute lung injury induced by pulmonary Escherichia coli instillation and the role of neutrophils in mediating this effect.

Design: Prospective randomized animal study.

Setting: University Research Laboratory.

Subjects: Adult male Sprague-Dawley rats.

Interventions: In series 1, after induction of anesthesia and tracheostomy placement, animals were randomized to normocapnia (Fico2 0.00, n = 12) or hypercapnic acidosis (Fico2 0.05, n = 12). E. coli (0.5–3.0 × 1015 colony-forming units) was instilled intratracheally and the animals were ventilated for 6 hrs to allow a severe acute lung injury to evolve. In series 2, animals were randomized to neutrophil depletion or nondepletion before bacterial instillation, in a three-group design: normocapnia alone (Normo + polymorphonuclear neutrophils [PMN], n = 9), normocapnia with neutrophil depletion (Normo − PMN, n = 9), or hypercapnic acidosis with neutrophil depletion (hypercapnic acidosis − PMN, n = 9). After intratracheal E. coli administration these animals were also ventilated for 6 hrs.

Results: Hypercapnic acidosis protected against evolving pneumonia-induced acute lung injury, attenuating the increase in airway pressure, and the decrement in lung compliance and arterial Po2. However, hypercapnic acidosis did not reduce histologic injury. Hypercapnic acidosis also protected against evolving pneumonia-induced acute lung injury in the presence of neutrophil depletion, reducing both physiologic and histologic indices of lung injury.

Conclusions: Hypercapnic acidosis reduces indices of intratracheal E. coli induced lung injury by a mechanism that seems to be neutrophil-independent.

From the Department of Anesthesia (MNC, BEH, JFC, JGL), Clinical Sciences Institute, National University of Ireland, Galway, and Lung Biology Group (MNC, BEH, JFC, JGL), National Centre for Biomedical Engineering Sciences, National University of Ireland, Galway, Ireland.

Supported, in part, by the Health Research Board, Ireland (MNC, BH, JGL) and by the Yamanouchi European Foundation (JGL). Dr. Ni Chonghaile is a clinical research fellow, and Dr. Higgins is a Postdoctoral Fellow, with the Health Research Board, Ireland.

Drs. Martina Ni Chonghaile and Brendan D. Higgins contributed equally to this work.

The authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: john.laffey@nuigalway.ie

© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins