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Clopidogrel induced suppression of bovine platelet activation in vitro and a preliminary study of its effect on the development of Mannheimia haemolytica induced pneumonia
Authors:Coomber Brenda L  Mitchell Gordon B  Starr Amanda E  Minhas Kanwal  Tamblyn Angela  Shewen Patricia E  Gentry Patricia A
Institution:Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ont., Canada N1G 2W1. bcoomber@uoguelph.ca
Abstract:We report here on the influence of the platelet antagonist clopidogrel (Plavix) on bovine platelet function. We first evaluated the capacity of clopidogrel to inhibit adenosine diphosphate (ADP)-stimulated platelet function in the bovine species, using an ex vivo approach with blood from treated animals. Platelets isolated from treated calves displayed rapid and consistent reduction in function (aggregation, thromboxane production) upon ADP, but not platelet activating factor (PAF), stimulation. We then examined the possibility that clopidogrel could influence Mannheimia haemolytica pneumonia pathobiology using an experimental challenge model. We were unable to detect significant differences between clopidogrel treated and untreated animals when challenged with intra-tracheal inoculation of M. haemolytica. There was a trend towards inhibition of platelet degranulation in the affected regions of lungs from clopidogrel treated calves, and pre-treated challenged animals had similar amounts of fibrin deposition and enhanced fibrous tissue formation in their lungs when compared with control counterparts.
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