Abstract
Platelet aggregation responses are conventionally assessed in cuvette-based systems using either isolated platelets or whole blood. Unfortunately, in vitro aggregometry poorly predicts in vivo functionality, since mediators derived from the vascular endothelium are major regulators of platelet function. There is a need, therefore, for functional assays that assess platelet responsiveness in vivo in the presence of an intact and functional vascular endothelium. We have developed methodology for monitoring aggregation responses of freely circulating radiolabelled platelets using external detection probes in the anaesthetised mouse. Intravenous injection of platelet agonists induces reversible, dose-dependent aggregation responses that are sensitive to anti-platelet therapies and modification of the vascular endothelium. The technique provides a means of determining the effects of pharmacological and genetic manipulation upon platelet function in vivo.
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References
Tymvios, C., et al., Real-time measurement of non-lethal platelet thromboembolic responses in the anaesthetized mouse. Thromb Haemost, 2008. 99: p. 435–440.
Morley, J. and C.P. Page, Platelet aggregometry in vivo. TiPS, 1984. 5: p. 258–60.
Nieswandt, B., et al., Platelets in atherothrombosis: lessons from mouse models. J Thromb Haemost, 2005. 3(8): p. 1725–36.
Bodary, P.F. and D.T. Eitzman, Animal models of thrombosis. Curr Opin Hematol, 2009. 16(5): p. 342–6.
Naseem, K.M. and R. Riba, Unresolved roles of platelet nitric oxide synthase. J Thromb Haemost, 2008. 6(1): p. 10–9.
Tymvios, C., et al., Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthase. Br J Pharmacol, 2009. 158(7): p. 1735–42.
Mitchell, J.A. and T.D. Warner, COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nat Rev Drug Discov, 2006. 5(1): p. 75–86.
May, G.R., et al., Radioisotopic model for investigating thromboembolism in the rabbit. J Pharmacol Methods, 1990. 24(1): p. 19–35.
Acknowledgements
Support for the work described in this chapter was provided by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (www.nc3rs.org.uk).
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Moore, C., Emerson, M. (2012). Assessment of Platelet Aggregation Responses In Vivo in the Mouse. In: Gibbins, J., Mahaut-Smith, M. (eds) Platelets and Megakaryocytes. Methods in Molecular Biology, vol 788. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-307-3_2
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DOI: https://doi.org/10.1007/978-1-61779-307-3_2
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