Cardiovascular protective role for activated protein C during endotoxemia in rats.
OBJECTIVE
We examined whether activated protein C (APC) treatment improves cardiovascular inflammation and dysfunction in endotoxemic rats.


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


METHODS
Male Sprague Dawley rats.


METHODS
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.


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.


CONCLUSIONS
APC reduces systemic and tissue inflammation and preserves cardiovascular function during experimental endotoxemia.
Favory
Raphael
R
EA 2689, Université de Lille 2, Faculté de Médecine Lille, Lille, France.
Lancel
Steve
S
Maréchal
Xavier
X
Tissier
Stéphanie
S
Neviere
Remi
R
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D019446:Endotoxemia; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D018046:Protein C Inhibitor / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D018046:Protein C Inhibitor; D015842:Serine Proteinase Inhibitors