Optimization of Multiplate® whole blood platelet aggregometry in the Beagle dog and Wistar rat for ex vivo drug toxicity testing
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Defontis, Myriam, Cote, Serge, Stirn, Martina and Ledieu, David (2012) Optimization of Multiplate® whole blood platelet aggregometry in the Beagle dog and Wistar rat for ex vivo drug toxicity testing. Experimental and Toxicologic Pathology. ISSN 0940-2993
Abstract
This study was performed to optimize and standardize the use of the Multiplate® whole blood impedance aggregometer in the Beagle dog and Wistar rat for use in a research laboratory environment. The anticoagulants citrate, heparin and hirudin were compared and platelet aggregation responses to ADP, collagen, arachidonic acid and Par-4 agonist were evaluated to determine their half maximal effective concentrations (EC50) in blood containing low concentrations of a drug solvent (0.1% DMSO). The results indicate that citrate anticoagulation is not suitable for Multiplate® whole blood aggregometry because of the presence of spontaneous aggregation. ADP and collagen were found to be appropriate agonists for both species, whereas in the Beagle dog Par-4 agonist failed to induce aggregation and arachidonic acid induced platelet aggregation showed a high interindividual variability. The agonists EC50 calculated in hirudin blood were 2.70μM ADP, 0.85μg/ml collagen, 0.03mM arachidonic acid and 165.7μM Par-4 agonist in the Wistar rat, and 0.95μM ADP and 0.23μg/ml collagen in the Beagle dog.
| Item Type: | Article |
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| Keywords: | aggregometry, agonist, anticoagulant, Beagle dog, Multiplate®, platelets, Wistar rat |
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| Date Deposited: | 13 Oct 2015 13:14 |
| Last Modified: | 13 Oct 2015 13:14 |
| URI: | https://oak.novartis.com/id/eprint/7759 |