Alprostadil: An Effective Antiplatelet Agent for Calves

Abstract

Aspirin and other nonsteroidal, antiinflammatory drugs inhibit human platelets, but their effect as an antiplatelet agent on bovine platelets is not certain. Since calves are used for cardiovascular implant research, need exists for an effective antiplatelet agent for this animal model. After screening a number of potential antiplatelet drugs for calves, Alprostadil (prostaglandin E1) appeared to be the most promising. Alprostadil was administered (intravenous continuous drip) to 8 calves. The concentration of the drug administered was gradually increased until 50% inhibition of platelet aggregation was obtained. Platelet function, blood pressure, body temperature, and hematologic parameters were closely monitored. For in vitro evaluation, Alprostadil was added to human or bovine blood, and the platelet aggregation and cyclic adenosine monophosphate levels were measured. Alprostadil inhibited both bovine and human platelets, although bovine platelets were relatively more responsive to this drug. At an infusion rate of approximately 0.20 micrograms/kg/min in vivo, Alprostadil showed 50% inhibition of platelet aggregation with slightly decreased blood pressure (7 +/- 6 mm Hg) but no adverse effects. Complete reversal of in vivo platelet inhibition was noted within 24 h after cessation of drug administration. This short half-life and the lack of significant adverse effects make Alprostadil an attractive antiplatelet agent for calves with cardiovascular implants.