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ABSTRACT-The effect of a chemically stable prostacyclin analog, OP-41483 a-cyclodextrin clathrate (OP-41483•a-CD), on vascular lesions, platelet aggregation and blood pressure were examined and compared with those of prostaglandin E1 a-cyclodextrin clathrate (PGE1.CD) in in vivo rat models. Prostacyclin is a chemically unstable compound that possesses both potent antiplatelet (1) and hypotensive (2) actions. Because of its clinical potential, various prostacyclin derivatives have been developed with the aims of increasing its chemical stability and dissociating these two actions. OP-41483•a-CD, 5(E)-6,9a methylene-15-cyclopentyl-16,17,18,19,20-pentanor-PG12 a-cyclodextrin clathrate, is a novel and chemically stable prostacyclin analog that inhibits platelet functions (adhesion and aggregation) and prevents thrombus formation in an electrically induced thrombus model in guinea pigs (3). The inhibitory effects of OP-41483•a CD on platelet functions are produced through dual mechanisms: one mediated by activation of adenylate cyclase and the other by inhibition of Ca 2+ influx (4). This compound also has a more potent antiplatelet effect than hypotensive activity in baboons (5) and hu mans (6). Therefore, OP-41483•a-CD may have anti thrombotic properties for the treatment of thrombotic and ischemic vascular diseases.In this study, we compared the inhibitory effect of OP-41483•a-CD with that of prostaglandin El a-cyclo dextrin clathrate (PGE1•CD) on two peripheral vascu lar lesion models in rats: the arterial thrombotic model induced by intraarterial injection of laurate and the vasoconstriction model induced by subcutaneous injec tion of epinephrine and ergotamine. Furthermore, the effects of both compounds on platelet aggregation (in vivo) and blood pressure were examined in conscious rats. MATERIALS AND METHODS AnimalsMale Wistar rats were purchased from Kitayama Labes and Shizuoka Laboratory Animal Center. All animals were kept in an animal room maintained at 24 ± 1°C with 60 ± 10% humidity and illuminated for 12 hr (8:00 AM-8:00 PM). They were fed a standard laboratory diet (Funabashi, MM-5) and tap water ad libitum.

1. A prospective clinical study of nonhemolytic hyperbilirubinemia in premature infants included 187 infants, of whom 100 had hyperbilirubinemia above 18 mg/100 ml and 87 had bilirubin levels never in excess of 15 mg/100 ml. In a random fashion, the infants with hyperbilirubinemia were divided evenly and either received replacement transfusions or did not. 2. Of the 50 infants in the exchange transfusion group, bilirubin levels were adequately controlled in 48 infants. There was no mortality associated with the exchange transfusion procedure. After 1 year, there does not appear to be any definite evidence of kernicterus in this group. 3. In the no-exchange group, 10 of the 50 infants had levels of bilirubin over 24 mg/ 100 ml for more than 48 hours. Of these, 1 developed fatal kernicterus. Eight of the other 9 infants, whose bilirubin values exceeded 24 mg/100 ml, and 32 of the original 40, whose bilirubin levels were over 18 but below 24 mg/100 ml, were examined neurologically after 1 year. No evidence of kernicterus was found. 4. Seventy-five of the 87 control infants were also examined neurologically after 1 year and none had evidence of kernicterus. 5. The evidence to date suggests that exchange transfusions in the management of non-hemolytic hyperbilirubinemia of the premature not associated with clinical factors which may enhance the development of kernicterus such as asphyxia, hypoproteinemia, sepsis, etc., need not be performed for unconjugated bilirubin values under 24 mg/100 ml. We believe that infants who will develop bilirubin levels in excess of 24 mg/100 ml may be anticipated if their plasma values exceed 20 mg/100 ml between 73 to 96 hours of age or 22 mg/100 ml between 96 and 120 hours. 6. The validity of these conclusions is dependent upon the long-term follow-up of these infants.