Erschienen in:
01.09.2005 | Experimental
Pretreatment with peroxysome proliferator-activated receptor α agonist fenofibrate protects endothelium in rabbit Escherichia coli endotoxin-induced shock
verfasst von:
Eric Wiel, Gilles Lebuffe, Emmanuel Robin, Gaëlle Gasan, Delphine Corseaux, Benoît Tavernier, Brigitte Jude, Régis Bordet, Benoît Vallet
Erschienen in:
Intensive Care Medicine
|
Ausgabe 9/2005
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Abstract
Objective
To investigate the effects of fenofibrate, an activator of peroxysome proliferator activated receptor (PPAR) α, on vascular endothelium and on hemostasis in a rabbit endotoxic shock model.
Design and setting
Prospective laboratory study in a university laboratory.
Subjects
36 male New Zealand rabbits weighing 2.5–3 kg.
Interventions
We determined in vitro vascular reactivity, endothelium CD31–platelet/endothelial cell adhesion molecule (PECAM) 1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor expression 5 days after onset of endotoxic shock (0.5 mg/kg intravenous bolus, Escherichia coli lipopolysaccharide) with or without treatment by fenofibrate (mixed in the chow at a concentration of 0.5%) for 15 days before lipopolysaccharide injection and 5 days afterward.
Measurements and results
Metabolic acidosis and coagulation activation confirmed presence of shock. Fenofibrate decreased monocyte tissue factor expression. It improved endothelial-dependent relaxation at 5 days (Emax=68.2±3.3%, vs. 44.2±2.5% in the non-treated group). Endotoxin-induced deendothelialization was significantly decreased by fenofibrate at 5 days (8.5±1.3% vs. 19.2±3.1% in the nontreated group).
Conclusions
These data indicate for the first time that fenofibrate, an activator of PPAR-α, inhibits monocyte tissue factor expression and protects against endothelial dysfunction and histological injury in endotoxin-induced shock.