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The role of thromboxane in verminous arteritis in horses

Cambridge, Heather (1989) The role of thromboxane in verminous arteritis in horses. PhD thesis, Murdoch University.

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Abstract

Severe mesenteric arteritis and thrombosis in horses produced by immature stages of the nematode parasite S. vulgaris can be accompanied by intestinal pain or colic. The pain is thought to result from intestinal ischaemia although the cause of ischaemia in naturally infected animals is unknown. Widespread embolisation is not a feature of the natural disease and the equine gut has unique anatomical features allowing compensation for occlusion of major vessels. Most infected animals are asymptomatic.

The work presented in this thesis results from an investigation of the hypothesis that thromboxane A2 (TXA2) produced by blood platelets may be important in the pathophysiology of clinical verminous arteritis. TXA2 is a powerful vasoconstrictor of blood vessels from many anatomical sites in a variety of species. Its other major biological property is enhancement of intravascular thrombosis by both direct activation of platelets and synergism with other platelet agonists.

The aim of the first aspect of the study was to establish whether peripheral levels of TXB2 (the stable breakdown product of TXA2) were elevated in animals experimentally infected with S. vulgaris. A radioimmunoassay was validated for use in unextracted horse plasma and levels in non-infected animals were found to be low. A total of 11 animals were studied, comprising 4 foals raised parasite free, 2 conventionally reared foals and 5 conventionally reared yearling horses. Lesions of severe arteritis were present at post mortem examination of all 6 foals but concurrent rises in TXB2 were not found. The yearling animals showed resistance to infection with only 1 developing arteritis. This animal was also clinically affected and mean levels of TXB2 after infection were significantly greater than in the control period.

Evidence for continuous TXA2 production could not be demonstrated, but significant local production of TXA2 within affected arteries seemed likely. The effects of vasoconstrictors on isolated strips of mesenteric and digital arteries and veins were compared to those produced by the stable endoperoxide/TXA2 analogue U46619. Contractions of equine digital arteries and veins were comparable to those produced by noradrenaline but equine mesenteric arteries were unresponsive to the endoperoxide analogue. Similar results were obtained in isolated perfused equine mesentery and hoof.

The effects of U46619, prostanoids, thromboxane synthase inhibiting drugs and thromboxane receptor antagonists on platelet aggregation were measured in vitro using a standard turbidimetric method. Unlike human platelets, equine platelets did not aggregate irreversibly in response to U46619 or arachidonic acid. Prostaglandins 12, D2 and E1 were found to be potent inhibitors of platelet aggregation.

The in vitro platelet aggregation experiments indicated that the arachidonate pathway may be less important in equine platelet function than in some other species, notably man. The correlation between increased skin bleeding time, a simple measure of in vivo platelet function, and suppression of thromboxane generation by aspirin was established. Bleeding time returned to normal limits significantly faster than the recovery of thromboxane generating capacity in aggregating platelets, demonstrating the compensatory effects by other pathways of platelet activation.

TXB2 has been reported to be chemotactic for inflammatory cells in other species and it was found to have weak chemotactic, but not chemokinetic, activity for equine isolated peripheral neutrophils and monocytes.

The lack of response of equine mesenteric vessels and platelets to thromboxane analogue indicates that TXA2 alone is unlikely to account for intestinal ischaemia in horses with verminous arteritis. Measurement of peripheral TXB2 is not a reliable marker for platelet activation in infected animals. By contrast this mediator seems likely to contribute to abnormal blood flow in the hoof in conditions such as endotoxaemia, where production of TXA2 is known to be increased and laminitis is a common sequela.

Item Type: Thesis (PhD)
Murdoch Affiliation: School of Veterinary Studies
Notes: Note to the author: If you would like to make your thesis openly available on Murdoch University Library's Research Repository, please contact: repository@murdoch.edu.au. Thank you.
Supervisor(s): Reynoldson, Jim
URI: http://researchrepository.murdoch.edu.au/id/eprint/53222
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