Platelet antagonists eliminate thromboembolic complications of small-diameter arterial prostheses

An animal model suitable for study of the origin and method of prevention of thromboembolic complications of arterial prostheses has been developed in the rabbit. In phase I of the experiments 42 New Zealand white rabbits underwent insertion of polytetrafluoroethylene (PTFE) aortic grafts, 10 mm in length and of 2 mm internal diameter (I.D.) (n = 17) and 3 mm I.D. (n = 25). The patency rate at 3 months was 24% and 82%, respectively. Unexpected ischemic hind limb ulcers occurred in nine (38%) of the long-term survivors. Arteriograms in these animals showed a typical embolic occlusion of a distal artery, suggesting that the ulcers were due to embolization of loose mural thrombus, which was present in 50% of the grafts when removed. In phase II experiments 54 rabbits were randomly allocated to receive aspirin (ASA) 10 mg/kg/day and dipyridamole (DPM) 10 mg/kg/day (n = 25) or placebo (n = 29). Both regimens began 3 days before insertion of PTFE aortic grafts (10 mm long and 3 mm I.D.). Serum thromboxane B2 concentrations in the control group averaged 300.4 +/- 147.4 ng/ml and 43.2 +/- 58.6 ng/ml in the ASA/DPM group (p less than 0.0005). With the use of autologous indium 111 oxine-labeled platelets, a graft platelet accumulation index (GPAI) was calculated as the graft: reference ratio of emissions. ASA/DPM significantly reduced the mean GPAI calculated from grafts and reference aorta removed 48 hours after graft insertion from 69.3 +/- 4.0 on placebo (n = 4) to 34.3 +/- 2.9 (n = 4) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)