Activated protein C increases sensitivity to vasoconstriction in rabbit Escherichia coli endotoxin-induced shock.
Crit Care
; 10(2): R47, 2006.
Article
en En
| MEDLINE
| ID: mdl-16542507
ABSTRACT
INTRODUCTION:
The aim of this study was to investigate the effects of activated protein C (aPC) on vascular function, endothelial injury, and haemostasis in a rabbit endotoxin-induced shock model.METHOD:
This study included 22 male New Zealand rabbits weighing 2.5 to 3 kg each. In vitro vascular reactivity, endothelium CD31-PECAM1 immunohistochemistry, plasma coagulation factors and monocyte tissue factor (TF) expression were performed 5 days (D5) after onset of endotoxic shock (initiated by 0.5 mg/kg intravenous bolus of Escherichia coli lipopolysaccharide (LPS)) with or without treatment with aPC injected as an intravenous 2 mg/kg bolus 1 hour after LPS (LPS+aPC group and LPS group, respectively).RESULTS:
LPS decreased the sensitivity to phenylephrine (PE) in aortic rings without endothelium (E-) when compared to E- rings from the control group (p < 0.05). This was abolished by NG-nitro-L-arginine methyl ester and not observed in E- rings from aPC-treated rabbits. Although aPC failed to decrease monocyte TF expression in endotoxinic animals at D5, aPC treatment restored the endothelium-dependent sensitivity in response to PE (2.0 +/- 0.2 muM in rings with endothelium (E+) versus 1.0 +/- 0.2 microM in E- rings (p < 0.05) in the LPS+aPC group versus 2.4 +/- 0.3 microM in E+ rings versus 2.2 +/- 0.2 microM in E- rings (p value not significant), in the LPS group). Endotoxin-induced de-endothelialisation was reduced by aPC at D5 (28.5 +/- 2.3% in the LPS+aPC group versus 40.4 +/- 2.4% in the LPS group, p < 0.05).CONCLUSION:
These data indicate that aPC increased the sensitivity to a vasoconstrictor agent (PE) associated with restoration of endothelial modulation, and protected against endothelial histological injury in endotoxin-induced shock. It failed to inhibit TF expression at D5 after LPS injection.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Choque Séptico
/
Vasoconstricción
/
Proteína C
/
Endotoxinas
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Crit Care
Año:
2006
Tipo del documento:
Article
País de afiliación:
Francia