REVERSIBLE BLOCKADE OF PLATELET ACTIVATION DURING CARDIO-PUIMONAR BYPASS IN DOGS AFTER IV ADMINISTRATION OF AJOENE
R Apitz Castro, E Ledezma, A Jorquera, M Jain
Surgery with extracorporeal circulation (ECC) is associated with platelet activation, which greatly contribute to prolonged postoperative bleeding and increased blood loss after surgery. Antiplatelet ccnpounds which induce rapid and reversible inhibition of platelet function, without affecting platelet adhesiveness would be potentially useful in the management of the platelet-dependent hemostatic disorder observed in ECC. Ajoene, an organosulfur originally obtained from garlic, inhibits
... release and aggregation induced ex vivo by all know agonists. It does not affect shape change or adhesion to collagen nor interfere with metabolic pathways relevant to the platelet reaction. Ajoene action is related to its direct interaction with the fibrinogen receptor on the platelet surface which irrpairs fibrinogen binding to stimulated or chymotrypsin treated platelets. IV administration of ajoene (15 mg/Kg) to mongrel dogs, inhibits platelet aggregation induced ex vivo by collagen (2-5 g/ml) or ADP (10 M). Ccnplete inhibition is attained after 20-35min and recuperation of platelet reactivity is obtained after 2.5-3.5 hours. To study the potential benefit of ajoene for the prevention of platelet activation during cardio-pulnonary bypass, ajoene was administered to anesthesized (heparin-anticoagulated) dogs, as described above, 40min before establishing the ECC. Circulation was mantained at 1.5L/min for a period of lOOmin Platelet count, and aggregation induced esc vivo by ADP or collagen were meassured immediately before ajoene administration, lOmin after the end of ECC and thereafter, hourly. Platelet count lOmin after end of ECC, in ncn-treated dogs fell to about 57% of prepump values, while in ajoene-treated animals circulating platelets represented 80% of pre-ECC values. Recovery of platelet function in ajoene-treated dogs started 2 hr after end of ECC (about 4 hr. after ajoene administration) reaching 70% 4 hr after end of ECC. Surgical bleeding in treated-dogs was not different frrm controls. Moderate bradicardia and hypotension, which in atrqpi-nized dogs returned to normal values within 3 min was observed. Although detailed pharmacological studies are still needed, our results suggest that ajoene is a potentially useful drug for the prevention of platelet activation induced by ECC.