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Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury

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Abstract

Objective

In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI.

Design and setting

Prospective, controlled study in an imaging facility.

Participants

Pigs tracheotomized and mechanically ventilated.

Intervention

Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid.

Measurements and results

Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO2 under FIO2 1 was significantly lower in the APC group before lung injury (473 ± 129 vs. 578 ± 54 mmHg) and 110 min (342 ± 138 vs. 446 ± 103 mmHg) and 290 min (303 ± 171 vs. 547 ± 54 mmHg) thereafter (p < 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0 ± 1.5 vs. 11.0 ± 2.5 ml/kg) (p > 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p < 0.05).

Conclusions

In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation–perfusion mismatch, with more perfusion to dependent nonaerated areas.

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Acknowledgements

This study received a grant of €25,679.70 from Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. Xigris® was provided by Lilly. Fabienne Bregeon was supported by a grant from the Laboratoires d'Explorations Fonctionnelles Respiratoires, Hôpital Nord, Marseille, France.

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Authors and Affiliations

  1. Service de Réanimation Médicale, Hôpital de la Croix Rousse, 103 Grande Rue de la Croix Rousse, 69004, Lyon, France

    Jean-Christophe Richard, Véronique Leray & Claude Guerin

  2. Claude Bernard University Lyon 1, 43 boulevard du 11 novembre 1918, 69622, Villeurbanne cedex, France

    Jean-Christophe Richard, Véronique Leray, Didier Le Bars, Nicolas Costes, Christian Tourvieille, Franck Lavenne, Mojgan Devouassoux-Shisheboran, Gerard Gimenez & Claude Guerin

  3. CREATIS CNRS UMR 5220-INSERM U 630, 7 rue Jean Capelle, batiment Blaise Pascal, 69621, Villeurbanne cedex, France

    Jean-Christophe Richard & Claude Guerin

  4. Laboratoire d’Explorations Fonctionnelles Respiratoires, Hôpital Nord, Marseille, France

    Fabienne Bregeon

  5. CERMEP Imagerie du Vivant, Lyon, France

    Didier Le Bars, Nicolas Costes, Christian Tourvieille, Franck Lavenne & Gerard Gimenez

  6. Laboratoire d’Anatomie Pathologique, Hôpital de la Croix Rousse, Lyon, France

    Mojgan Devouassoux-Shisheboran

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  1. Jean-Christophe Richard
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Correspondence to Claude Guerin.

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This article is discussed in the editorial available at: http://dx.doi.org/10.1007/s00134-007-0783-z.

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Richard, JC., Bregeon, F., Leray, V. et al. Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury. Intensive Care Med 33, 2199–2206 (2007). https://doi.org/10.1007/s00134-007-0782-0

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  • DOI: https://doi.org/10.1007/s00134-007-0782-0

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