Combined arachidonic acid and ADP platelet inhibition maximizes patency of small-diameter vascular grafts.
Arachidonic acid (AA) and adenosine diphosphate (ADP) are potent stimuli of platelet aggregation. Each agonist may act through separate platelet pathways. In order to evaluate inhibition of ADP and AA on platelet aggregation, we studied the effect of ticlopidine (TC) and aspirin (ASA) alone and in combination on plasma thromboxane levels, platelet deposition, and patency of small-diameter vascular grafts in a canine model. Thirty-four mongrel dogs were classified as thrombosis prone (TP) or thrombosis resistant (TR) on the basis of in vitro platelet aggregation to AA. Four groups were studied: group I, control; group II, TC (100 mg/kg/day); group III, ASA (3 mg/kg/day); and group IV, TC/ASA (same doses). PTFE grafts were implanted bilaterally in the carotid and femoral arteries Ticlopidine inhibited in vitro platelet aggregation to both ADP and AA but had no significant effect on plasma thromboxane (Tx) B2 production. Aspirin inhibited AA-induced platelet aggregation and significantly decreased TxB2 production. Aspirin inhibited AA-induced platelet aggregation and significantly decreased TxB2 levels in both TP and TR animals (p less than 0.01). Although TC and ASA significantly inhibited platelet deposition and improved 1-month patency in both TP and TR animals, maximal patency was achieved in the group in which TC and ASA were combined. We conclude that platelet ADP and AA pathways are important determinants of the thrombogenic potential in vascular graft performance in dogs and that combined inhibition of both pathways achieves maximal vascular graft patency.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001807:Blood Vessel Prosthesis; D002339:Carotid Arteries / Q000601:surgery; D004285:Dogs; D005263:Femoral Artery / Q000601:surgery; D010974:Platelet Aggregation / Q000187:drug effects*; D011138:Polytetrafluoroethylene; D013929:Thromboxane B2 / Q000097:blood; D013988:Ticlopidine / Q000494:pharmacology; D014654:Vascular Patency / Q000187:drug effects*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D011138:Polytetrafluoroethylene; D013988:Ticlopidine; D001241:Aspirin