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 factor (PDGF), on anastomotic intimal hyperplasia and platelet aggregation. Twenty Beagle dogs underwent infrarenal aortic reconstruction with an expanded polytetrafluoroethylene (ePTFE) graft 5 mm in diameter and 3 cm long. The dogs were divided into three groups: placebo (control group, 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 operation and once daily for 3 months after operation. Grafts were harvested 3 months after operation. All 13 grafts in the treated groups remained 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 hyperplasia at the anastomoses. The platelet aggregation ratio (PAR) with collagen (100 micrograms/ml) before drug administration at 3 months in the 4-mg group was significantly lower than that in the control and 1-mg groups. PAR after drug administration at 3 months in the 1- and 4-mg groups was significantly lower than that in the control group. Intimal thickness at the distal anastomosis was 817 +/- 190 microns in the control group, 240 +/- 80 microns in the 1-mg group, and 197 +/- 28 microns in the 4-mg group. Intimal thickness in the control group was significantly greater than that in the 1- and 4-mg groups. Smooth muscle cell (SMC) values in the intima at the distal anastomosis were 65.6 +/- 4.4% extinction (%E) in the control group, 47.6 +/- 3.4%E in the 1-mg group, and 51.3 +/- 3.5%E in the 4-mg group. SMC value in the control group was significantly greater than that in the 1- and 4-mg groups. E5510 inhibited PAR and reduced the degree of anastomotic intimal hyperplasia.
Fujioka
K
K
First Department of Surgery, Yamaguchi University School of Medicine, Japan.
Esato
K
K
Furutani
A
A
Akiyama
N
N
Yoshimura
K
K
Takenaka
H
H
Sekido
T
T
Suganuma
A
A
Sagami
F
F
D000714:Anastomosis, Surgical / Q000009:adverse effects*; D000818:Animals; D001011:Aorta / Q000473:pathology* / Q000601:surgery; D001792:Blood Platelets / Q000187:drug effects; D004285:Dogs; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; C054678:Satigrel