beraprost and Hyperplasia

Hemodialysis vascular access dysfunction, mostly attributed to neointimal hyperplasia, is a major cause of morbidity and hospitalization in patients on hemodialysis. It has been reported that prostaglandin I. Fifty-five patients with end-stage renal disease who were on hemodialysis were prospectively selected for this study. Twenty-three patients were assigned to be treated with 120 µg/day of beraprost sodium, while remaining patients (n = 32) were assigned to a control group. The primary outcome was primary unassisted vascular access patency at 2 years.. The incidence of primary unassisted patency at 2 years was 83% in the beraprost sodium group and 38% in the control group (p = 0.001). Analysis of covariables indicated that this effect occurred mainly as a result of beraprost sodium administration. No life-threatening adverse event or severe bleeding was recorded in any of the groups.. Our data indicated that an oral prostaglandin I

Topics: Aged; Arteriovenous Shunt, Surgical; Epoprostenol; Female; Humans; Hyperplasia; Kidney Failure, Chronic; Male; Middle Aged; Neointima; Platelet Aggregation Inhibitors; Prospective Studies; Renal Dialysis; Secondary Prevention; Time Factors; Vascular Patency

1. The aim of the present study was to evaluate the inhibitory effects of the short-term administration of beraprost sodium, a stable prostaglandin I(2) analogue, on neointimal thickening after stenting. 2. To examine the immediate and short-term effects, Z-stents were placed in the iliac veins of 12 dogs, which were randomly assigned to either a beraprost-treated or control (saline) group. Beraprost (0.35 microg/kg per min) or saline (1.5 mL/min) was administered 30 min before stenting and was continued for 5 h thereafter. Platelet aggregation was measured before and after drug administration. At 3, 7 and 14 days after stenting, dogs were killed and immunohistochemical staining for proliferating cell nuclear antigen was used to quantify the proliferation of vascular smooth muscle cells (SMC). To evaluate intermediate-term effects, a Z-stent was placed in the right iliac vein in 10 dogs, followed by beraprost treatment. Three days later, a second Z-stent was placed contralaterally with saline infusion as a control. After 4 weeks, dogs were killed and neointimal thickness was measured under a light microscope to calculate the intima : media area ratio. 3. Platelet aggregation was more significantly suppressed in the beraprost-treated than in the control group (P = 0.01). In addition, SMC proliferation was significantly lower in the beraprost-treated group 7 and 14 days after stenting (P < 0.05). Over the intermediate term, the intima : media area ratio was significantly lower in the beraprost-treated vein compared with control (P < 0.05). 4. In conclusion, short-term beraprost treatment during stenting suppresses in situ platelet aggregation and SMC proliferation, thus reducing neointimal thickening.

Topics: Animals; Blood Vessel Prosthesis; Cell Proliferation; Dogs; Epoprostenol; Graft Occlusion, Vascular; Hyperplasia; Infusions, Intravenous; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Platelet Aggregation; Platelet Aggregation Inhibitors; Time Factors; Tunica Intima; Tunica Media

The aim of this study was to evaluate the effect of a novel prostaglandin I2 analogue, beraprost (BPT), on the pseudointimal hyperplasia (PIH) of polytetrafluoroethylene (PTFE) prostheses. A total of 12 rabbits were equally divided into three groups. The control group was given a placebo daily, group 1 was given BPT orally 2 mg/kg per day, and group 2 was given BPT orally 4 mg/kg b.i.d. Exactly 1 cm of the inferior vena cava was resected and replaced by a 3-cm PTFE tube graft. All the grafts were patent when harvested 4 weeks after implantation, but the lumens were narrowed to various extents by PIH. PIH, determined by the dry weight of the intraluminal tissue deposit, was significantly (P < 0.01) suppressed in groups 1 and 2 compared with the control group. High-magnification light microscopy with various staining methods revealed the PIH to be composed mainly of smooth muscle cells (SMCs) and collagen fibrils in all three groups. Transmission electron microscopy revealed that the majority of SMCs in groups 1 and 2 were contractile in form, in contrast with the synthetic form seen in the control group. In conclusion, BPT attenuated the PIH of PTFE grafts by inhibiting the phenotype change in the SMCs.

Topics: Animals; Blood Vessel Prosthesis; Epoprostenol; Growth Inhibitors; Hyperplasia; Microscopy, Electron; Microscopy, Electron, Scanning; Muscle, Smooth, Vascular; Polytetrafluoroethylene; Rabbits; Tunica Intima

The effects of beraprost sodium, a stable analogue of prostacyclin, on the syntheses of DNA, protein and glycosaminoglycans (GAG) of cultured vascular smooth muscle cells (SMC) were studied. SMC were isolated from the thoracic aorta of male Wistar rats. The syntheses of DNA, protein and GAG of SMC were determined by incorporations of [3H]thymidine, [3H]leucine and [35S]sulfuric acid, respectively. Insulin at a concentration of 10(-6) M stimulated DNA synthesis 4 fold compared to control. Beraprost sodium suppressed the insulin-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 68% at 10(-5) M. Platelet derived growth factor (PDGF) at a concentration of 20 ng/ml stimulated DNA synthesis 6 fold compared to control. Beraprost sodium suppressed the PDGF-stimulated DNA synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 51% at 10(-5) M. Beraprost sodium suppressed GAG synthesis dose-dependently at concentrations greater than 10(-7) M and suppressed it by 49% at 10(-5) M. However, beraprost sodium at concentrations up to 10(-5) M did not affect protein synthesis. These results indicate that beraprost sodium suppressed the proliferation and GAG synthesis of SMC but did not affect hypertrophy. Beraprost sodium may be a potent antiarteriosclerotic agent through suppression of hyperplasia of SMC and modification of matrix protein.

Topics: Animals; Aorta, Thoracic; Cell Division; Cells, Cultured; DNA; Epoprostenol; Glycosaminoglycans; Growth Inhibitors; Hyperplasia; Hypertrophy; Insulin; Male; Muscle Proteins; Muscle, Smooth, Vascular; Platelet-Derived Growth Factor; Rats; Rats, Wistar