Antagonism of endotoxin-induced disruption of equine gastrointestinal motility with the platelet-activating factor antagonist WEB 2086.

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.