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Cardiovascular protective role for activated protein C during endotoxemia in rats

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Abstract

Objective

We examined whether activated protein C (APC) treatment improves cardiovascular inflammation and dysfunction in endotoxemic rats.

Design and setting

Randomized, controlled trial in an experimental laboratory of a university physiology department

Subjects

Male Sprague Dawley rats.

Interventions

Internal carotid artery and external jugular vein were catheterized under sterile conditions in rats. Instrumented rats infused or not with APC (240 μg/kg per hour) were challenged with E. coli endotoxin (10 mg/kg). Four hours after endotoxin challenge rats were prepared for cardiovascular functional studies and tissue and blood analyses.

Measurements and results

Endotoxin administration induced systemic hypotension, depression of myocardial systolic performance and reduction in capillary density of the small intestine muscularis layer. Plasma levels of nitrite/nitrate, tumor necrosis factor α and macrophage migration inhibitory factor, mesentery venule leukocyte-endothelium interactions, heart and small intestine myeloperoxidase activities were increased in endotoxin-treated rats. APC largely prevented endotoxin-induced cardiovascular dysfunction with improved systemic hemodynamics, functional capillary density, and myocardial contractile performance. Beneficial cardiovascular effects of APC were associated with attenuation of entotoxin-induced inflammatory response in terms of plasma levels of nitrite/nitrate, tumor necrosis factor α, macrophage migration inhibitory factor, and endothelial cell–leukocyte activation.

Conclusion

APC reduces systemic and tissue inflammation and preserves cardiovascular function during experimental endotoxemia.

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Authors and Affiliations

  1. Faculté de Médecine Lille, EA 2689, Université de Lille 2, Lille, France

    Raphael Favory, Steve Lancel, Xavier Maréchal, Stéphanie Tissier & Remi Neviere

  2. Département de Physiologie, Faculté de Médecine 1, Place Verdun, 59045, Lille, France

    Steve Lancel, Xavier Maréchal & Remi Neviere

Authors
  1. Raphael Favory
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  2. Steve Lancel
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  3. Xavier Maréchal
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  4. Stéphanie Tissier
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  5. Remi Neviere
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Corresponding author

Correspondence to Remi Neviere.

Additional information

This research was funded in part by Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Ind., USA, in the form of a research grant totaling €27,000 and the provision of rat recombinant protein C (drotecogin alpha).

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Favory, R., Lancel, S., Maréchal, X. et al. Cardiovascular protective role for activated protein C during endotoxemia in rats. Intensive Care Med 32, 899–905 (2006). https://doi.org/10.1007/s00134-006-0166-x

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  • DOI: https://doi.org/10.1007/s00134-006-0166-x

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