title: Optimization of Multiplate(®) whole blood platelet aggregometry in the Beagle dog and Wistar rat for ex vivo drug toxicity testing.
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 (EC(50)) 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 EC(50) calculated in hirudin blood were 2.70 μM ADP, 0.85 μg/ml collagen, 0.03 mM arachidonic acid and 165.7 μM Par-4 agonist in the Wistar rat, and 0.95 μM ADP and 0.23 μg/ml collagen in the Beagle dog.
authors.affiliation: Department of Veterinary Clinical Sciences, Clinical Pathology and Clinical Pathophysiology, Justus-Liebig University Giessen, Frankfurterstrasse 126, 35392 Giessen, Germany. m_defontis@hotmail.com
authors.forename: Myriam
authors.initials: M
authors.lastname: Defontis
authors.forename: Serge
authors.initials: S
authors.lastname: Côté
authors.forename: Martina
authors.initials: M
authors.lastname: Stirn
authors.forename: David
authors.initials: D
authors.lastname: Ledieu
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D004285:Dogs; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000379:methods* / Q000592:standards; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D010975:Platelet Aggregation Inhibitors