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Treatment with anti-factor VIIa in acute pancreatitis in rats: Blocking both coagulation and inflammation?

Andersson, Ellen LU ; Axelsson, Jakob B LU ; Pedersen, Lars Christian; Elm, Torben and Andersson, Roland LU (2007) In Scandinavian Journal of Gastroenterology 42(6). p.765-770
Abstract
Objective. Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active- siteinactivated factor VIIa, have shown anti- inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome ( MODS) in severe acute pancreatitis. Material and methods. Experimental acute pancreatitis was induced by intraductal infusion of... (More)
Objective. Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active- siteinactivated factor VIIa, have shown anti- inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome ( MODS) in severe acute pancreatitis. Material and methods. Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N- acetyl- cysteine and active- site- inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL- 6 and MIP- 2, were measured using ELISA. Results. Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N- acetylcysteine and active- site- inactivated factor VIIa. Levels of interleukin- 6 and macrophage inflammatory protein- 2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels. Conclusions. Both N- acetylcysteine and active- site- inactivated factor VIIa showed powerful antiinflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Gastroenterology
volume
42
issue
6
pages
765 - 770
publisher
Taylor & Francis
external identifiers
  • wos:000246766600014
  • scopus:34248593271
ISSN
1502-7708
DOI
10.1080/00365520701295632
language
English
LU publication?
yes
id
554183b8-37c6-4748-b2ba-f34ef6a2a8c9 (old id 168263)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17506000&dopt=Abstract
date added to LUP
2007-07-20 14:41:38
date last changed
2017-02-26 04:06:28
@article{554183b8-37c6-4748-b2ba-f34ef6a2a8c9,
  abstract     = {Objective. Acute pancreatitis starts as an autodigestive process restricted to the pancreas and progresses to a systemic inflammation via cytokine release into the blood stream. Several inhibitors of the coagulation cascade, including active- siteinactivated factor VIIa, have shown anti- inflammatory properties in other inflammatory models than acute pancreatitis. Free radical scavengers have proven useful in reducing the oxidative damage during hyperinflammatory conditions. The aim of this study was to investigate whether pretreatment with FVIIai would have any effect on the multiple organ dysfunction syndrome ( MODS) in severe acute pancreatitis. Material and methods. Experimental acute pancreatitis was induced by intraductal infusion of taurodeoxycholate in the pancreatic duct. The animals were pretreated with N- acetyl- cysteine and active- site- inactivated factor VIIa. Neutrophil infiltration in the lungs, ileum and colon was quantified by myeloperoxidase activity. Inflammatory markers, IL- 6 and MIP- 2, were measured using ELISA. Results. Tissue infiltration of neutrophils in the lungs, ileum and colon significantly increased during acute pancreatitis as compared to sham operation. These levels were reduced by pretreatment with N- acetylcysteine and active- site- inactivated factor VIIa. Levels of interleukin- 6 and macrophage inflammatory protein- 2 increased significantly during acute pancreatitis. Pretreatment with NAC and FVIIai reduced these levels. Conclusions. Both N- acetylcysteine and active- site- inactivated factor VIIa showed powerful antiinflammatory properties in experimental acute pancreatitis. As they exert their effects through different physiological mechanisms, they represent potential candidates for future multimodal treatment of acute pancreatitis.},
  author       = {Andersson, Ellen and Axelsson, Jakob B and Pedersen, Lars Christian and Elm, Torben and Andersson, Roland},
  issn         = {1502-7708},
  language     = {eng},
  number       = {6},
  pages        = {765--770},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {Treatment with anti-factor VIIa in acute pancreatitis in rats: Blocking both coagulation and inflammation?},
  url          = {http://dx.doi.org/10.1080/00365520701295632},
  volume       = {42},
  year         = {2007},
}