Arterial wall thromboxane: dominance after surgery predisposes to thrombosis

Ibuprofen reduces early occlusion and surface thrombogenicity of small-diameter polytetrafluoroethylene (PTFE) grafts in sheep. The following experiments were designed to determine the effects of cyclooxygenase inhibition by ibuprofen on long-term patency and arterial wall and graft neointima prostaglandin synthesis. Crossover PTFE grafts (internal diameter 4 mm) were interposed between the carotid arteries of 18 sheep. Nine animals were used as controls, and nine received ibuprofen, 10 mm/kg intravenously, 1 hour prior to surgery and then every 8 hours for the duration of the experiment. Grafts were removed either when they became occluded or routinely at 60 days. Arterial segments adjacent to anastomoses were removed at graft insertion and at graft removal for assay of arterial wall production of the prostaglandins 6-keto-PGF1 alpha and thromboxane B2 (TxB2). There was no difference in patency between control animals (four out of nine) and ibuprofen-treated (five out of nine) animals. Arterial segments removed before the administration of ibuprofen produced 2.59 +/- 1.48 nM/mg protein/20 min of 6-keto-PGF1 alpha and 2.59 +/- 1.38 nM/mg protein/20 min of TxB2. A single dose of ibuprofen reduced the levels of 6-keto-PGF1 alpha to 0.30 +/- 0.12 nM/mg protein/20 min and the levels of TxB2 to 0.78 +/- 0.41 nM/mg protein/20 min (p less than 0.01). When the grafts were removed, control animals showed a reduction of 6-keto-PGF1 alpha to 1.69 +/- 0.86 nM/mg protein/20 min, whereas TxB2 levels remained unchanged at 2.54 +/- 1.23 nM/mg protein/20 min.(ABSTRACT TRUNCATED AT 250 WORDS)