EFFECT OF E5510 ON ANASTOMOTIC INTIMAL HYPERPLASIA AND PLATELET-AGGREGATION IN DOGS

We examined the effect of an antiplatelet agent, E5510, which inhibits both platelet aggregation and release of platelet-derived growth fact or (PDGF), on anastomotic intimal hyperplasia and platelet aggregation . Twenty Beagle dogs underwent infrarenal aortic reconstruction with a n expanded polytetrafluoroethylene (ePTFE) graft 5 mm in diameter and 3 cm long. The dogs were divided into three groups: placebo (control g roup, 7 dogs), E5510 1 mg/day (1-mg group, 6 dogs), and E5510 4 mg/day (4-mg group, 7 dogs). E5510 was administered orally 2 h before operat ion and once daily for 3 months after operation. Grafts were harvested 3 months after operation. All 13 grafts in the treated groups remaine d patent without evidence of intimal hyperplasia, whereas only 4 of 7 grafts (57 %) remained patent in the control group, including 1 graft with > 50 % stenosis. Three occluded grafts showed severe intimal hype rplasia at the anastomoses. The platelet aggregation ratio (PAR) with collagen (100 mu g/ml) before drug administration at 3 months in the 4 -mg group was significantly lower than that in the control and 1-mg gr oups. PAR after drug administration al 3 months in the 1- and 4-mg gro ups was significantly lower than that in the control group, Intimal th ickness at the distal anastomosis was 817 +/- 190 mu m in the control group, 240 +/- 80 mu m in the 1-mg group, and 197 +/- 28 mu m in the 4 -mg group. Intimal thickness in the control group was significantly gr eater than that in the 1- and 4-mg groups. Smooth muscle cell (SMC) va lues in the intima at the distal anastomosis were 65.6 +/- 4.4 % extin ction (%E) in the control group, 47.6 +/- 3.4 %E in the 1-mg group, an d 51.3 +/- 3.5 %E in the 4-mg group, SMC value in the control group wa s significantly greater than that in the 1-and 4-mg groups. E5510 inhi bited PAR and reduced the degree of anastomotic intimal hyperplasia.