The effect of clinical prostacyclin infusions in advanced arterial disease on platelet function and plasma 6-keto PGF1 alpha levels.
We have infused synthetic prostacyclin (PGI2) continuously for approximately 72 h at the maximum tolerated dose (ranging from 5 to 60 ng/kg/min) into nine patients with advanced arterial disease. Prior to the infusion seven out of nine patients  had spontaneous platelet aggregation and five out of six patients tested had an abnormal circulating platelet aggregate ratio. During the infusion only one patient still had spontaneous aggregation and all the abnormal circulating platelet aggregate ratios returned to the normal range. However, none of the patients showed any suppression of ADP induced aggregation. The level of exogenous PGI2 required in vitro prior to the infusion to completely inhibit ADP induced aggregation was 5-10 ng/ml in three of the four patients tested. Ten healthy adults showed complete inhibition with 1 ng/ml of PGI2. It appears that the platelets of some patients with arterial disease are more resistant to the anti-aggregating properties of PGI2. Plasma 6-keto PGF1 alpha levels, measured by radioimmunoassay, were within the normal range (100-381 pg/ml) in all but one of the patients prior to the infusion. During the infusion plasma 6-keto PGF1 alpha levels rose proportionally to the infusion dose. After stopping the infusion 6-keto PGF1 alpha levels declined according to an exponential process with a half life of 18-29 min, prolonged to 47 min in one patient who was anuric. The linear increase in 6-keto PGF1 alpha levels suggests this as a useful indicator of increased circulating PGI2.
D000328:Adult; D000368:Aged; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000188:drug therapy*; D011464:Epoprostenol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011460:Prostaglandins F / Q000097:blood*; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use*; D013997:Time Factors
D011460:Prostaglandins F; D011465:Prostaglandins, Synthetic; D011464:Epoprostenol