Peripheral Vascular Studies in Sheep With Reference to the Pathophysiology of Laminitis

Pawson, Patricia Edith (1998) Peripheral Vascular Studies in Sheep With Reference to the Pathophysiology of Laminitis. PhD thesis, University of Glasgow.

Abstract

Altered blood flow to the foot contributes to the syndrome of laminitis, an important cause of lameness in domestic ungulates. Factors such as vasoconstriction, arteriovenous shunting and microthrombosis are believed to reduce perfusion within the hoof leading to ischaemic tissue damage. Endothelium-derived mediators, such as nitric oxide and prostacyclin, have a key role in the modulation of local vascular tone and alterations in the production of these agents could contribute to the vascular derangements observed in laminitis. In this study, the sheep was used as a model for both equine and bovine laminitis. The responses of isolated ovine digital arteries to vasoconstrictor and vasodilator agents were studied in vitro and the effects of endothelium-removal, nitric oxide synthase inhibition and/or cyclooxygenase inhibition were studied. The response to phenylephrine, an alpha1-adrenergic agonist, was found to be modulated by vasodilatory prostanoids, whilst relaxation to bradykinin was mediated by a combination of endothelium-derived nitric oxide and prostanoids. Both endotoxin and cytokines have been implicated in the pathogenesis of laminitis, therefore digital artery vascular responses were also examined following a 6 or 16 hour incubation with these agents. Incubation with endotoxin did not significantly alter the dose-response curves to phenylephrine or bradykinin. However, incubation for 6 hours with interferon-gamma and tumour necrosis factor-alpha did significantly increase the maximum relaxation to bradykinin. Furthermore, a 16 hour incubation with interferon-gamma, interleukin 1-beta and tumour necrosis factor-alpha significantly increased the EC50 of the response to phenylephrine, i.e. decreased the sensitivity to this vasoconstrictor. Thus, the vascular responsiveness of ovine digital arteries may be altered by cytokines in vitro and further work is needed to determine the mechanism of these alterations. The second part of this project sought to evaluate limb blood flow in the live animal, thereby allowing for the influence of the hoof. The shape of the velocity-time waveform of an artery changes in response to alterations in downstream resistance or impedance and such changes in shape can be quantified by calculation of the pulsatility index. In this study, the femoral artery velocity waveform was examined and the response to infusion of vasoactive agents was described in terms of the pulsatility index. Pulsatility index rose in response to infusion of phenylephrine. However, there was also a tendency for pulsatility index to rise, mainly from an increase in reflected velocities, on infusion of the vasodilator sodium nitroprusside. This unexpected result implies that the blood flow response to intense vasodilation is modified in the intact animal, possibly by the hoof.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Andrea Nolan
• Keywords: Veterinary science, Animal diseases
• Date of Award: 1998
• Depositing User: Enlighten Team
• Unique ID: glathesis:1998-75880
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 17:40
• Last Modified: 19 Nov 2019 17:40
• URI: https://theses.gla.ac.uk/id/eprint/75880