The effect of thromboxane a2 systhesis inhibitors on platelet aggregation in whole blood

Inhibitory effect of a selective thromboxane A2receptor antagonist, EP 092, on platelet aggregation in whole bloodex vivoandin vivo

“…In the ex vivo studies with guinea-pig and Rhesus monkey citrated whole blood, collagen caused concentration-dependent aggregatory responses reflected in a rapid decrease in single platelet count detectable within 1-2min. The range of collagen concentrations at which an aggregatory response was observed was similar to that observed previously for both rodent and human blood (Saniabadi et al, 1983;Lad et al, 1987). Administration of EP 092 to guinea-pigs or Rhesus monkeys potently inhibited collagen-induced aggregatory responses in whole blood ex vivo, indicating a significant role for PGH2 and TXA2 in these responses.…”

“…Rhesus monkey platelets synthesize TXB2 in response to addition of arachidonic acid (Gorman et al, 1983) or collagen (our data), and are susceptible to inhibition of U-44069-induced aggregation in PRP responses ex vivo by the PGH2/TXA2 receptor antagonist L-655240 (Hall et al, 1987). In the present experiments, Rhesus monkey platelets in whole blood responded with a sensitivity to collagen (EC50 0.48 + 0.4 Mg ml-1) almost identical to that of human whole blood under the same experimental conditions (EC50 0.53 + 0.1pgmlmP; Lad et al, 1987).…”

“…The method employed for monitoring platelet aggregatory responses in guinea-pig and Rhesus monkey whole blood was a modification of the single platelet counting technique first described by Nunn & White (1980) which we have described previously (Lad et al, 1987). Briefly, each 0.5 ml aliquot of citrated blood was stirred in a 1 ml aggregation cuvette at 1000 r.p.m.…”

“…In the present study, we chose to investigate the ability of EP 092 to inhibit collagen-induced whole blood platelet aggregatory responses ex vivo using a single platelet counting technique (Lad et al, 1987) in citrated blood samples obtained from guinea-pigs or Rhesus monkeys pretreated with EP 092. These experiments prompted an examination of the effect of EP 092 on collagen and thrombin-induced intravascular aggregation in the anaesthetized rabbit by continuous platelet count monitoring in vivo (Honey et al, 1986).…”

<i>In vitro</i> canine platelet aggregation caused by <i>Dirofilaria immitis</i> extract

“…To examine the involvement of COX-dependent pathways and the ADP receptor on canine platelet aggregation induced by a HW extract, the following tests were conducted. Firstly, after the pre-incubation of indomethacin (300 µ M) [ 11 ] at 37°C for 3 min, platelet aggregation was initiated by the addition of 22 µl of HW extract stock solution or 10 µ g/m l (final concentration) of collagen (control) and monitored for 5 min. Next, ATP, an antagonist of P2Y (ADP) receptor, was pre-incubated with PRP at a final concentration of 1 mM for 3 min [ 9 ].…”