Antagonism of endotoxin-induced disruption of equine gastrointestinal motility with the platelet-activating factor antagonist WEB 2086.
Abstract: The effect of pre-treatment with a selective platelet-activating factor (PAF) antagonist, WEB 2086, on the actions of low-dose endotoxin was evaluated in ponies prepared with gastrointestinal strain gauges. Endotoxin (0.1 microgram/kg i.v.) produced a marked reduction in gastric contraction amplitude and rate, and an increased frequency and reduced duration of jejunal phase III activity fronts (AFs). WEB 2086 (6.6 mg/kg) administered i.v. 10 min before the endotoxin, produced significant antagonism (P less than 0.001) of the effect of endotoxin on gastric contraction amplitude and rate. The combination of WEB 2086 and endotoxin produced gastric contractions of significantly (P less than 0.01) higher frequency than in the control studies. WEB 2086 also reduced endotoxin-induced abnormal phase III AFs in the jejunum and increases in heart rate and packed cell volume. These results provide evidence that endogenous PAF plays a role in mediating the acute effects of endotoxin on equine gastrointestinal motility.
Publication Date: 1990-12-01 PubMed ID: 2287025DOI: 10.1111/j.1365-2885.1990.tb00786.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigated the impact of using a platelet-activating factor antagonist, WEB 2086, as a pre-treatment against endotoxin disruption in ponies’ gastrointestinal motility. The results supported the hypothesis that endogenous PAF is involved in mediating the acute effects of endotoxin on equine gastrointestinal motility.
Study Background
- The objective of the research was to examine the influence of a selective platelet-activating factor (PAF) antagonist, WEB 2086, on low-dose endotoxin’s effects in ponies, focusing specifically on equine gastrointestinal motility.
Research Methodology
- The ponies in the study were prepared with gastrointestinal strain gauges, tools used to measure mechanical forces in the gastrointestinal tract, before the administration of endotoxin.
- The researchers administered endotoxin in a low dose (0.1 microgram/kg) intravenously.
- The treatment significantly reduced gastric contraction amplitude and rate, and also induced an increased frequency and reduced duration of jejunal phase III activity fronts – periods of strong, regular contractions in the small intestine.
- 10 minutes before the endotoxin introduction, the researchers administered WEB 2086 (6.6 mg/kg) intravenously as a pre-treatment.
Research Findings
- Throughout the study, WEB 2086 significantly antagonized
(end-resisted) the effect of endotoxin on gastric contraction amplitude and rate. - A statistically significant higher frequency of gastric contractions was noted in the group pre-treated with WEB 2086 and exposed to endotoxin compared to control studies.
- The use of WEB 2086 also mitigated the abnormal phase III activity fronts (AFs) in the jejunum induced by endotoxin, as well as endotoxin-related increases in heart rate and packed cell volume (the volume percentage of red blood cells in blood).
- These results suggested that the endogenous PAF – a type of phospholipid that activates platelets and has various physiological properties – mediates the acute effects of endotoxin on equine gastrointestinal motility.
Cite This Article
APA
King JN, Gerring EL.
(1990).
Antagonism of endotoxin-induced disruption of equine gastrointestinal motility with the platelet-activating factor antagonist WEB 2086.
J Vet Pharmacol Ther, 13(4), 333-339.
https://doi.org/10.1111/j.1365-2885.1990.tb00786.x Publication
Researcher Affiliations
- Department of Surgery and Obstetrics, Royal Veterinary College, North Mymms, Herts, UK.
MeSH Terms
- Animals
- Azepines / pharmacology
- Endotoxins / antagonists & inhibitors
- Endotoxins / pharmacology
- Gastrointestinal Motility / drug effects
- Heart Rate / drug effects
- Hematocrit / veterinary
- Horses / physiology
- Leukocyte Count / drug effects
- Leukocyte Count / veterinary
- Male
- Muscle Contraction / drug effects
- Platelet Activating Factor / antagonists & inhibitors
- Stomach / drug effects
- Stomach / physiology
- Triazoles / pharmacology
Citations
This article has been cited 3 times.- Lautenschläger I, Frerichs I, Dombrowsky H, Sarau J, Goldmann T, Zitta K, Albrecht M, Weiler N, Uhlig S. Quinidine, but not eicosanoid antagonists or dexamethasone, protect the gut from platelet activating factor-induced vasoconstriction, edema and paralysis. PLoS One 2015;10(3):e0120802.
- Koenig J, Cote N. Equine gastrointestinal motility--ileus and pharmacological modification. Can Vet J 2006 Jun;47(6):551-9.
- Navarre CB, Roussel AJ. Gastrointestinal motility and disease in large animals. J Vet Intern Med 1996 Mar-Apr;10(2):51-9.
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