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Cardiovascular protective role for activated protein C during endotoxemia in rats.

Authors: Favory, R  Lancel, S  Marechal, X  Tissier, S  Neviere, R 
Citation: Favory R, etal., Intensive Care Med. 2006 Jun;32(6):899-905. Epub 2006 Apr 7.
Pubmed: (View Article at PubMed) PMID:16601957
DOI: Full-text: DOI:10.1007/s00134-006-0166-x

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 microg/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 alpha 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 alpha, 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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RGD Object Information
RGD ID: 1641983
Created: 2007-08-27
Species: All species
Last Modified: 2007-08-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.