Inhibitory effects of alprostadil (prostaglandin E1) incorporated in lipid microspheres of soybean oil on intimal hyperplasia following balloon injury in rabbits.

The present study was performed to assess the inhibitory effects of alprostadil (CAS 745-65-3, prostaglandin E 1 , PGE 1 ) incorporated in lipid microspheres (hereinafter referred to as lipo PGE 1 ; Palux® inj.) on intimal thickening following balloon injury in the carotid artery of normal rabbits. Lipo PGE 1 was given intravenously to animals twice a day at doses of 20 or 40 μg/kg/day from ballooning (day 1) until day 3, and at half these doses from day 4 to day 20. The carotid artery was removed for histopathological staining on the next day (day 21) after the last administration. Lipo PGE 1 significantly reduced both the intimal/medial area (I/ M) ratio and stenosis ratio by about half in the 40 μg/kg/day on day 21 after ballooning, compared with the vehicle group. Infiltration of macrophage, expression of proliferating cell nuclear antigen (PCNA)-positive cells was inhibited by the administration of lipo PGE 1 on day 3 after ballooning. Adhesion of platelets to injured arterial walls was also inhibited on day 3. Lipo PGE 1 at 40 μg/kg/ day exerted more potent inhibitory effects on I/M and stenosis ratios and histopathological changes such as infiltration of macrophage and expression of PCNA-positive cells than at 20 μg/kg/day. These findings suggest that lipo PGE 1 inhibits the intimal hyperplasia after balloon injury in rabbit carotid artery, possibly by inhibiting platelet functions.