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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/L718    most recent 90298.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Eckle, T. Articles by Eltzschig, H. K. PubMed PubMed Citation Articles by Eckle, T. Articles by Eltzschig, H. K.

INNOVATIVE METHODOLOGY

Usefulness of pressure-controlled ventilation at high inspiratory pressures to induce acute lung injury in mice

Departments of ¹Anesthesiology and Intensive Care Medicine, and ³Pharmacology and Toxicology, Tübingen University Hospital, Tübingen, Germany; and ²Mucosal Inflammation Program, Department of Anesthesiology and Perioperative Medicine, University of Colorado Health Sciences Center, Denver, Colorado

Submitted 3 May 2008 ; accepted in final form 14 August 2008

ABSTRACT

Acute lung injury (ALI), as occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation. Here, we systematically tested a murine model of ALI by using pressure-controlled ventilation to induce ventilator-induced lung injury. For this purpose, C57BL/6 or Sv129 mice were anesthetized and underwent tracheotomy followed by induction of ALI via mechanical ventilation. Mice were ventilated in a pressure-controlled setting at different inspiratory pressure levels (15–45 mbar) and over different times (0–90 min, 100% oxygen). As outcome parameters, we assessed pulmonary edema (wet-to-dry ratios), bronchoalveolar fluid albumin content, pulmonary myeloperoxidase activity, macrophage inflammatory protein-2, and pulmonary gas exchange. These studies revealed maximal differences in severity of lung injury between different mouse strains after 90 min of ventilation time at 45 mbar. Use of lower concentrations of inspired oxygen did not alter disease severity. Increases of CD73 transcript (5'-ectonucleotidase, pacemaker of extracellular adenosine production) or total pulmonary adenosine levels with mechanical ventilation were less pronounced in C57BL/6 mice, suggesting attenuated adenosine protection in C57BL/6 mice. Together, these studies demonstrate feasibility of this model to induce murine ALI.

ventilator-induced lung injury