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Treatment with the sphingosine-1-phosphate analogue FTY 720 reduces loss of plasma volume during experimental sepsis in the rat.

Lundblad, Cornelia LU ; Axelberg, Helén LU and Grände, Per-Olof LU (2013) In Acta Anaesthesiologica Scandinavica 57(6). p.713-718
Abstract
BACKGROUND: Increased vascular leakage leading to hypovolaemia and tissue oedema is common in severe sepsis. Hypovolaemia together with oedema formation may contribute to hypoxia and result in multiorgan failure and death. To improve treatment during sepsis, a potential therapeutic target may be to reduce the vascular leakage. Substances affecting the endothelial barrier are interesting in this respect, as it is suggested that increase in vascular leakage depends on reorganisation of the endothelial cells and breakdown of the endothelial barrier. The agonist of the bioactive lipid sphingosine-1-phosphate, FTY720, has been shown to modulate the integrity of the endothelium and reduce permeability both in vitro and in vivo. The aim of the... (More)
BACKGROUND: Increased vascular leakage leading to hypovolaemia and tissue oedema is common in severe sepsis. Hypovolaemia together with oedema formation may contribute to hypoxia and result in multiorgan failure and death. To improve treatment during sepsis, a potential therapeutic target may be to reduce the vascular leakage. Substances affecting the endothelial barrier are interesting in this respect, as it is suggested that increase in vascular leakage depends on reorganisation of the endothelial cells and breakdown of the endothelial barrier. The agonist of the bioactive lipid sphingosine-1-phosphate, FTY720, has been shown to modulate the integrity of the endothelium and reduce permeability both in vitro and in vivo. The aim of the present study was to determine if FTY720 could reduce the loss of plasma volume during experimental sepsis in rats. METHODS: Sepsis was induced by ligation and incision of the caecum in the rat. Plasma volume was determined before and 4.5 h after induction of sepsis by a dilution technique using (125) I-labelled albumin. RESULTS: FTY720 in a dose of 0.2 mg/kg reduced the loss of plasma during sepsis by approximately 30% compared with vehicle, without any adverse effects on haemodynamic and physiological parameters. The increase in hematocrit and haemoglobin concentration was also found to be higher in the vehicle group. CONCLUSION: FTY720 in a dose without haemodynamic side effects reduces loss of plasma volume during experimental sepsis most likely because of reduction in permeability and may therefore be beneficial in sepsis. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Anaesthesiologica Scandinavica
volume
57
issue
6
pages
713 - 718
publisher
Wiley-Blackwell
external identifiers
  • wos:000320116800006
  • pmid:23683126
  • scopus:84878826618
  • pmid:23683126
ISSN
0001-5172
DOI
10.1111/aas.12130
language
English
LU publication?
yes
id
b1c546ac-1a12-4f3a-8013-78babf222eb6 (old id 3804379)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23683126?dopt=Abstract
date added to LUP
2016-04-01 11:00:58
date last changed
2022-01-26 04:48:10
@article{b1c546ac-1a12-4f3a-8013-78babf222eb6,
  abstract     = {{BACKGROUND: Increased vascular leakage leading to hypovolaemia and tissue oedema is common in severe sepsis. Hypovolaemia together with oedema formation may contribute to hypoxia and result in multiorgan failure and death. To improve treatment during sepsis, a potential therapeutic target may be to reduce the vascular leakage. Substances affecting the endothelial barrier are interesting in this respect, as it is suggested that increase in vascular leakage depends on reorganisation of the endothelial cells and breakdown of the endothelial barrier. The agonist of the bioactive lipid sphingosine-1-phosphate, FTY720, has been shown to modulate the integrity of the endothelium and reduce permeability both in vitro and in vivo. The aim of the present study was to determine if FTY720 could reduce the loss of plasma volume during experimental sepsis in rats. METHODS: Sepsis was induced by ligation and incision of the caecum in the rat. Plasma volume was determined before and 4.5 h after induction of sepsis by a dilution technique using (125) I-labelled albumin. RESULTS: FTY720 in a dose of 0.2 mg/kg reduced the loss of plasma during sepsis by approximately 30% compared with vehicle, without any adverse effects on haemodynamic and physiological parameters. The increase in hematocrit and haemoglobin concentration was also found to be higher in the vehicle group. CONCLUSION: FTY720 in a dose without haemodynamic side effects reduces loss of plasma volume during experimental sepsis most likely because of reduction in permeability and may therefore be beneficial in sepsis.}},
  author       = {{Lundblad, Cornelia and Axelberg, Helén and Grände, Per-Olof}},
  issn         = {{0001-5172}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{713--718}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Acta Anaesthesiologica Scandinavica}},
  title        = {{Treatment with the sphingosine-1-phosphate analogue FTY 720 reduces loss of plasma volume during experimental sepsis in the rat.}},
  url          = {{http://dx.doi.org/10.1111/aas.12130}},
  doi          = {{10.1111/aas.12130}},
  volume       = {{57}},
  year         = {{2013}},
}