PROSTACYCLIN PRODUCTION IN THE AREA OF ARTERIAL ENDOTHELIAL DENUDATION

The goal of this study was to quantify arterial prostacyclin (PGI2) synthesis and platelet aggregation in the immediate area of vessel injury. Twelve mongrel dogs whose platelets aggregated maximally to added arachidonic acid (AA) were equally divided into three groups. Controls received no drug while other dogs were treated with the platelet inhibitors aspirin (ASA) 3 mg/kg/day or BM 13.505 (BM), a thromboxane receptor antagonist, 25 mg/kg/day. After 3 days of treatment, the dogs underwent balloon catheter endothelial denudation of both carotid and femoral arteries. Blood was sampled from the first carotid artery just distal to the injury at 0, 1, 5, and 10 min after restoration of flow. Venous blood samples were also obtained at 1 and 2 weeks postoperatively. Dogs were sacrificed at 2 weeks and arterial rings from a proximal normal and a denuded region were excised and tested for PGI2 production in response to added AA. While control dogs showed no statistical change in AA-induced platelet aggregation postoperatively, there appeared to be a trend for enhanced responsiveness at 1 week. Aspirin and BM inhibited AA-induced aggregation completely in all samples at all timepoints. Levels of the stable metabolite of PGI2, 6-keto-PGF1α, were determined by radio-immunoassay. In control dogs, baseline PGI2 levels were 72 ± 17 pg/ml which increased to 479 ± 20 pg/ml immediately after restoration of flow (P < 0.001, Student t test) and returned to basal values in 10 min (85 ± 5 pg/ml). Although ASA treatment did not lower basal PGI2 levels (66 ± 8 pg/ml), it completely prevented the injury-induced PGI2 burst, 68 ± 22 vs 479 ± 20 pg/ml (P < 0.001, Student t test). With BM, basal PGI2 levels were unaffected (84 ± 20 pg/ml). Notably, however, the injury-induced PGI2 burst still occurred in the presence of BM (427 ± 114 pg/ml; P < 0.05, Student t test). Analysis of arterial segments revealed that deendothelialization resulted in a significant, consistent reduction in PGI2 production in arterial segments from control (36%), aspirin (42%), and BM treated dogs (46%) (P < 0.02, two-way ANOVA). These findings demonstrate that: (1) a burst in PGI2 levels occurs in the immediate area of arterial injury; (2) ASA does not lower basal PGI2, but it completely blocks the injury-induced PGI2 burst; and (3) BM does not alter basal PGI2 and allows the PGI2 burst to occur. Inhibition of the PGI2 burst in the area of vessel injury may be an undesirable effect of ASA treatment. © 1991.