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-PGF1 alpha, were determined by radioimmunoassay. In control dogs, baseline PGI2 levels were 72 +/- 17 pg/ml which increased to 479 +/- 20 pg/ml immediately after restoration of flow (P less than 0.001, Student t test) and returned to basal values in 10 min (85 +/- 5 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Schwarcz
T H
TH
Department of Surgery, University of Illinois College of Medicine, Chicago.
Eton
D
D
Ellenby
M I
MI
Dieter
J
J
Dy
J
J
Tessalee
M
M
Shrader
D
D
LeBreton
G C
GC
D000818:Animals; D001158:Arteries / Q000293:injuries* / Q000378:metabolism; D002404:Catheterization / Q000009:adverse effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D008297:Male; D010974:Platelet Aggregation; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D011464:Epoprostenol