Pharmacologic modification of acute vascular graft thrombosis.
A baboon arteriovenous shunt model has been used to study acute vascular graft thrombosis, and to assess the effectiveness of various antithrombotic agents. External velour Dacron (Sauvage) vascular grafts, placed inside Teflon tubing to prevent blood leakage, were interposed between lengths of a Silastic, femoral arteriovenous shunt. After thirty minutes exposure to flowing blood, specimens were removed for evaluation by scanning electron microscopy (SEM). Antithrombotic agents, given singly and in combination, included heparin, the potent platelet inhibitor prostacyclin (PGI2), and the snake venom ancrod (which selectively degrades circulating fibrinogen). Control graft surfaces showed uniform coverage by thrombus with masses of red cells and platelets entrapped in fibrin mesh. Extensive platelet deposition was not prevented by either heparin or PGI2, although heparinized animals showed little fibrin accumulation. Similarly, platelet deposition was extensive in animals receiving ancrod, singly or in combination with PGI2, despite the absence of circulating fibrinogen. Thrombus accumulation was effectively prevented only by heparin in combination with PGI2, demonstrating that in this setting, thrombosis may be initiated by either platelet or coagulation-dependent mechanisms that do not require circulating fibrinogen or its conversion to morphologically detectable amounts of fibrin. These mechanisms remain to be characterized. Two control grafts evaluated at one week showed complete surface coverage by macrophages, and the flow surface appeared nonthrombogenic despite significant underlying thrombus.
D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D001792:Blood Platelets / Q000648:ultrastructure; D011464:Epoprostenol / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000637:transplantation* / Q000648:ultrastructure; D010215:Papio; D011453:Prostaglandins / Q000494:pharmacology*; D013927:Thrombosis / Q000209:etiology*
D011453:Prostaglandins; D006493:Heparin; D011464:Epoprostenol