title: 5-HT2a receptor antagonism reduces burn-induced macromolecular efflux in rats.
abstract: BACKGROUND
  Major thermal injuries lead to a systemic inflammatory response with systemic capillary leakage and multiple organ dysfunction. This systemic inflammatory response is induced by a variety of immunmodulative molecules including TNFα and serotonin. Unspecific serotonin antagonism leads to reduced macromolecular efflux in rat mesenteries after burn plasma transfer. The aim of the present study was to evaluate the effect of specific 5-HT2a antagonism on early burn edema.
  
  
  METHODS
  Donor rats (DR) underwent thermal injury (100 °C water, 30% BSA, 12 s) for positive controls. For negative controls, DR underwent sham burn (37 °C water, 30% BSA, 12 s). DR plasma (harvested 4 h post-trauma) was transferred to healthy individuals for positive controls. Study rats received burn plasma (BP) and a Bolus injection of Ketanserin (Ket) (1 mg kg(-1) body weight). Negative controls underwent sham burn plasma infusion. Intravital microscopy was performed in mesenteric venules (0/60/120 min). Edema was assessed by FITC-albumin extravasation. Additionally, leukocyte rolling and sticking (cells mm(-2)) as well as microhemodynamic parameters were assessed.
  
  
  RESULTS
  Significant systemic capillary leakage was observed after BP transfer at 120 min and additional administration of Ket attenuated the postburn edema to sham burn levels. Ket also leads to significantly decreased leukocyte-endothelial interactions when compared to positive controls.
  
  
  CONCLUSIONS
  5-HT2a antagonism reduces plasma extravasation after burn plasma transfer in healthy individuals. The influence of leukocyte-endothelial interactions on postburn edema remains unclear.
authors.affiliation: BG Trauma Center Ludwigshafen, Ludwigshafen, Germany. jfhernekamp@bgu-ludwigshafen.de.
authors.forename: J F
authors.initials: JF
authors.lastname: Hernekamp
authors.affiliation: BG Trauma Center Ludwigshafen, Ludwigshafen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Klein
authors.affiliation: BG Trauma Center Ludwigshafen, Ludwigshafen, Germany.|Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: BG Trauma Center Ludwigshafen, Ludwigshafen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Kneser
authors.affiliation: BG Trauma Center Ludwigshafen, Ludwigshafen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kremer
mesh_terms: D000818:Animals; D002056:Burns / Q000503:physiopathology*; D004487:Edema / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology; D008643:Mesentery / Q000502:physiology; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D012709:Serum Albumin; D007650:Ketanserin
keywords: Burns; Intravital microscopy; Ketanserin; Plasma extravasation; Rats