title: Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses.
abstract: BACKGROUND
  Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis.
  
  
  OBJECTIVE
  Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro.
  
  
  METHODS
  Twelve healthy horses received an i.v. infusion either of saline or a phospholipid emulsion (100 mg/kg), followed immediately by E. coli 055:B5 LPS (30 ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and severity of haemolysis were monitored before and at selected times after LPS. Monocytes were also incubated in vitro with LPS in the presence or absence of emulsion, after which TNF and tissue factor activities were determined.
  
  
  RESULTS
  Clinical signs of endotoxaemia were reduced in horses receiving the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the characteristic leucopenic response to LPS, when compared to horses not receiving the emulsion. Three horses receiving the emulsion had none, 2 had mild and one had moderate haemolysis. There were no differences in urinalysis results and creatinine concentrations, either within the groups over time or between the groups. Serum concentrations of phosphatidylcholine, bile acids and triglycerides peaked immediately after the infusion; there were no significant changes in concentrations of nonesterified fatty acids or cholesterol. Incubation of equine monocytes with emulsion prevented LPS-induced TNF and tissue factor activities.
  
  
  CONCLUSIONS
  Rapid administration of emulsion significantly reduced inflammatory effects of LPS in vivo and caused a clinically insignificant degree of haemolysis. The results of the in vitro studies indicate that emulsion prevents not only LPS-induced synthesis of cytokines, but also expression of membrane-associated mediators (i.e. tissue factor).
  
  
  CONCLUSIONS
  Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses.
authors.affiliation: College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Moore
authors.forename: N
authors.initials: N
authors.lastname: Norton
authors.forename: M H
authors.initials: MH
authors.lastname: Barton
authors.forename: D J
authors.initials: DJ
authors.lastname: Hurley
authors.forename: A J
authors.initials: AJ
authors.lastname: Reber
authors.forename: D C
authors.initials: DC
authors.lastname: Donovan
authors.forename: M L
authors.initials: ML
authors.lastname: Vandenplas
authors.forename: T S
authors.initials: TS
authors.lastname: Parker
authors.forename: D M
authors.initials: DM
authors.lastname: Levine
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000628:therapy / Q000662:veterinary*; D005217:Fat Emulsions, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D006734:Horse Diseases / Q000139:chemically induced / Q000628:therapy*; D006736:Horses; D007262:Infusions, Intravenous / Q000662:veterinary; D007700:Kinetics; D008297:Male; D010743:Phospholipids / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005217:Fat Emulsions, Intravenous; D010743:Phospholipids