Effects of low-dose aspirin and specific thromboxane synthetase inhibition on whole blood platelet aggregation and adenosine triphosphate secretion in healthy dogs

Abstract

SUMMARY Platelet aggregation and adenosine triphosphate (atp) secretion in response to arachidonic acid (10 μM) or collagen (5 μg/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, po, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, po, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P < 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P < 0.001) decreased platelet atp secretion in response to arachidonic acid, compared with baseline values; however atp secretion in aspirin-treated dogs was significantly (P < 0.01) less than atp secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet atp secretion was significantly (P < 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage. After a single orally administered dosage of 10 mg of CGS 12970/kg, platelet aggregation was maximally inhibited at 1 hour, remained negligible through 12 hours, and returned to normal by 96 hours. Platelet numbers were not affected by treatment with CGS 12970. These results indicate that similar to low-dose aspirin administration, treatment with CGS 12970 decreases arachidonic acid-induced, but not collagen-induced, whole blood platelet aggregation in dogs. Low-dose aspirin administration, however, was more effective than CGS 12970 treatment in reducing arachidonic acid- and collagen-induced platelet atp secretion.