Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses.
Abstract: 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.
Publication Date: 2007-05-25 PubMed ID: 17520976DOI: 10.2746/042516407x173343Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research tested whether quickly administering a lower dose of phospholipid emulsions, which bind to endotoxins, could help combat endotoxaemia in horses, causing less haemolysis (destruction of red blood cells). The results showed that the emulsions noticeably reduced the damaging effects of endotoxaemia and caused a minimal degree of haemolysis, suggesting it could offer a new treatment method for endotoxaemia.
Objective and Methods
- The researchers aimed to determine whether rapidly administering a smaller overall dose of a phospholipid emulsion could lessen the effects of endotoxin (LPS), which causes endotoxaemia, and result in less haemolysis. They also aimed to test whether this emulsion could reduce the inflammatory effects of LPS in vitro (in a lab environment).
- To carry out this study, they gave twelve healthy horses either a saline solution or a phospholipid emulsion (100 mg/kg) via intravenous (i.v.) infusion. This was followed immediately by the administration of E. coli 055:B5 LPS (30 ng/kg).
- Various parameters were monitored before and at select times after the LPS was administered to track the effects of the emulsion. These included clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and the severity of haemolysis.
- They also tested the effects of the emulsion on monocytes (a type of white blood cell) in vitro with LPS, after which they measured the TNF and tissue factor activities.
Results
- The tests revealed that clinical signs of endotoxaemia were reduced in horses that had been given the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the leucopenic response (decrease in the number of white blood cells) to LPS.
- Three of the horses that got the emulsion had no haemolysis, two had mild haemolysis, and one had moderate haemolysis.
- There were no differences in the urinalysis results and creatinine concentrations over time or between the groups.
- Levels of phosphatidylcholine, bile acids, and triglycerides reached their peak right after the infusion. However, there were no significant changes in the concentrations of nonesterified fatty acids or cholesterol.
- When equine monocytes were incubated with the emulsion in vitro, the emulsion prevented LPS-induced TNF and tissue factor activities.
Conclusions
- The rapid administration of the phospholipid emulsion significantly reduced the inflammatory effects of LPS and only caused a small degree of haemolysis.
- The results of the in vitro tests suggest that the emulsion not only prevents the cytokine synthesis induced by LPS but also the expression of associated membrane mediators (i.e., tissue factor).
- The research concluded that rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses.
Cite This Article
APA
Moore JN, Norton N, Barton MH, Hurley DJ, Reber AJ, Donovan DC, Vandenplas ML, Parker TS, Levine DM.
(2007).
Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horses.
Equine Vet J, 39(3), 243-248.
https://doi.org/10.2746/042516407x173343 Publication
Researcher Affiliations
- College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA.
MeSH Terms
- Animals
- Area Under Curve
- Body Temperature / drug effects
- Dose-Response Relationship, Drug
- Endotoxemia / therapy
- Endotoxemia / veterinary
- Fat Emulsions, Intravenous / adverse effects
- Fat Emulsions, Intravenous / therapeutic use
- Female
- Heart Rate / drug effects
- Hemolysis / drug effects
- Horse Diseases / chemically induced
- Horse Diseases / therapy
- Horses
- Infusions, Intravenous / veterinary
- Kinetics
- Male
- Phospholipids / adverse effects
- Phospholipids / therapeutic use
- Severity of Illness Index
- Time Factors
- Treatment Outcome
Citations
This article has been cited 7 times.- Mukhopadhyay A, Cook SR, SanMiguel P, Ekenstedt KJ, Taylor SD. TLR4 and MD2 variation among horses with differential TNFα baseline concentrations and response to intravenous lipopolysaccharide infusion. Sci Rep 2023 Jan 27;13(1):1486.
- Scavone D, Sgorbini M, Borges AS, Oliveira-Filho JP, Vitale V, Paltrinieri S. Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia. BMC Vet Res 2020 Nov 4;16(1):422.
- Bauquier J, Tudor E, Bailey S. Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses. J Vet Intern Med 2020 Sep;34(5):2109-2116.
- Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A. Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys. J Vet Intern Med 2020 Jul;34(4):1631-1641.
- Vinther AM, Skovgaard K, Heegaard PM, Andersen PH. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation. BMC Vet Res 2015 Jun 16;11:134.
- Arnob A, Gairola A, Clayton H, Jayaraman A, Wu HJ. Factors Promoting Lipopolysaccharide Uptake by Synthetic Lipid Droplets. ACS Omega 2025 Feb 18;10(6):5866-5873.
- Arnob A, Gairola A, Clayton H, Jayaraman A, Wu HJ. Factors Promoting Lipopolysaccharide Uptake by Synthetic Lipid Droplets. bioRxiv 2024 Oct 19;.
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