Objective To investigate the effects of Rho-kinase inhibitor——fasudil hydrochloride hydrate on vein graft intimal hyperplasia in vivo. Methods Twenty-four healthy rabbits (2.3-2.5 kg) were randomly divided into two groups(n=12). Fasudil hydrochloride hydrate (experimental group) and normal sodium (control group) were given 3 days beforeoperation with 30 mg/kg by intravenous injection everyday and continued until the end of the experiment. After a longitudinal incision, the femoral vein and the famoral artery were exposed about 3 cm. An approximately 2.5 cm segment of the famoral vein was harvested for the reversed-vein graft. The femoral artery was removed 1 cm segment and replaced by the harvested femoral vein. At 2 and 4 weeks after operation, the grafts were stained with HE to observe the thickness of the intima. Furthermore, the prol iferating cell nuclear antigen (PCNA) and transmission electron microscope was used to study the prol iferation of smooth muscle cell. In situ apoptosis was detected by TUNEL assay. Results All rabbits survived till the end of the experiment. The color Doppler imaging examination showed that all grafts were patency. At 2 and 4 weeks after the operation, HE staining showed that the intimal hyperplasia were obvious in the two groups. There were lots of cells in the intima, and more fusiform smooth muscle cells in the media. At 2 and 4 weeks, the intimal thickness were (30.33 ± 3.23) μm and (43.11 ± 4.92) μm in experimental group and were (44.83 ± 3.53) μm and (66.16 ± 8.45) μm in control group. The rates of PCNA positive cell were 14.28% ± 2.76% and 7.61% ± 1.06% in experimental group and were 20.08% ± 3.56% and 8.73% ± 1.35% in control group. The rates of TUNEL positive cell were 3.55% ± 0.36% and 1.22% ± 0.18% in experimental group and were 1.11% ± 0.31% and 0.55% ± 0.11% in control group. There were significant differences (P lt; 0.05) between the two groups at 2 weeks or 4 weeks, between2 weeks and 4 weeks within group. Conclusion Intravenous injection of fasudil hydrochloride hydrate is an effective method for prevention of vein graft intimal hyperplasia of rabbit.
Objective To assess the effect of topical appl ication of 5-fluorouracil (5-FU) on intimal hyperplasia in rabbit vein graft. Methods Sixty-four male New Zealand white rabbits, aged 5 months and weighing 2.8-3.0 kg, were randomly divided into group A, B, C, and D (n=16 rabbits per group). Artery defect model was establ ished by cutting about 1 cm artery from the middle part of the dissociated left common carotid artery. A section about 3 cm was cut from the right external jugular vein, and the harvested vein was inverted and end-to-end anastomosed to the artery defect with 9-0 non-traumatic suture. After anastomosis, the extima of the grafted veins in group A, B, and C was completely wrapped with cotton sheet (12 mm × 30 mm × 1 mm in size) immersed by 5-FU at a concentration of 50.0, 25.0, and 12.5 mg/mL, respectively, and eachvein was treated 5 times (1 minute at a time). In group D, the extima of the graft veins was treated with normal sal ine instead of 5-FU. The grafted veins were obtained 1, 2, 4, and 6 weeks after operation, HE staining and Masson staining were preformed for histological changes of grafted vein wall, prol iferating cell nuclear antigen (PCNA) immunohistochemistry staining and TUNEL label ing staining were conducted for prol iferation and apoptosis of smooth muscle cell of the grafted vein, and transmission electron microscope observation was performed for cellular ultrastructure. Results The HE staining, Masson staining, and PCNA immunohistochemistry staining showed that the thickness of intima in group A and B was obviously less than that in group C and D at 1, 2, 4, and 6 weeks after operation, and the prol iferation cells in group A and B were less than that in group C and D at 1, 2, and 4 weeks after operation. The thickness of the intima, the degree of intima hyperplasia, the degree of vessel lumen stenosis of four groups at different time points were as follows: at 1 week after operation, group A [(12.69 ± 1.68) μm, 0.73 ± 0.05, 0.025 ± 0.003], group B [(17.52 ± 2.01) μm, 0.86 ± 0.06, 0.027 ± 0.004], group C [(21.92 ± 1.85) μm, 1.06 ± 0.09, 0.036 ± 0.006] and group D [(26.45 ± 3.86) μm, 1.18 ± 0.08, 0.041 ± 0.005]; at 2 weeks after operation, group A [(24.61 ± 2.91) μm, 0.86 ± 0.06, 0.047 ± 0.003], group B [(37.28 ± 2.78) μm, 1.17 ± 0.09, 0.060 ± 0.004], group C [(46.52 ± 2.25) μm, 1.44 ± 0.08, 0.073 ± 0.003], and group D [(52.07 ± 3.29) μm, 1.45 ± 0.05, 0.081 ± 0.006]; at 4 weeks after operation, group A [(61.09 ± 6.84) μm, 1.38 ± 0.08, 0.106 ± 0.007], group B [(63.61 ± 8.25) μm, 1.40 ± 0.07, 0.107 ± 0.010], group C [(80.04 ± 7.65) μm, 1.64 ± 0.07, 0.129 ± 0.011], and group D [(84.45 ± 9.39) μm, 1.68 ± 0.10, 0.139 ± 0.014]; at 6 weeks after operation, group A [(65.27 ± 5.25) μm, 1.46 ± 0.07, 0.113 ± 0.005], group B [(65.82 ± 7.12) μm, 1.45 ± 0.05, 0.112 ± 0.011], group C [(84.45 ± 9.39) μm, 1.69 ± 0.09, 0.135 ± 0.007], and group D [(87.27 ± 8.96) μm, 1.76 ± 0.05, 0.140 ± 0.012]. Group A and B were inferior to group C and D in terms of the above three parameters and cell prol iferation index 1, 2 and 4 weeks after operation (P lt; 0.05). Group A and B were superior to group C and D in terms of cell apoptosis index of intima and media 1 and 2 weeks after operation (P lt; 0.05). Transmission electron microscope observation showed that the synthetic cell organelles such as rough endoplasmic reticulum, golgi apparatus, and ribosome in group A and B were obviously less than those in group C and D (P lt; 0.05). Conclusion Topicalappl ication of 5-FU can effectively inhibit intima hyperplasia of the vein grafts.
To evaluate the effect of 5-fluorouracil (5-FU) appl ied topically on preventing adhesion andpromoting functional recovery after tendon repair. Methods From August 2003 to June 2007, 48 patients with flexor tendonrupture of the fingers by sharp instrument were treated and randomly divided into two groups. In 5-FU group, 39 fingers of 26 patients included 17 males and 9 females, aged (29.3 ± 9.8) years; the locations were zone I in 19 fingers and zone II in 20 fingers; single finger was involved in 12 cases and more than 2 fingers were involved in 14 cases; and the time from injury to operation was (2.4 ± 1.6) hours. In control group, 36 fingers of 22 patients included 14 males and 8 females; aged (26.1 ± 8.7) years; the locations were zone I in 16 fingers and zone II in 20 fingers; single finger was involved in 10 cases and more than 2 fingers were involved in 12 cases; and the time from injury to operation was (2.1 ± 1.8) hours. No statistically significant difference was found in constituent ratio of age, gender, injured fingers and their zones, between two groups (P gt; 0.05). The repair site in 5-FU group was given 5-FU at a concentration of 25 mg/mL with a soaked sponge, and the synovial sheath of the repaired site was wrapped with the 5-FU-soaked sponge for 1 minute for 4 times after the tendons were repaired; normal sal ine was used in the control group. Results Wound healed by first intention and no infection and tendon rupture occurred in two groups. The patients were followed up for 3-8 months (mean 4.1 months) and 3-8 months (mean 3.9 months) in 5-FU group and in control group respectively. The functional recovery degrees of the fingers were evaluated with total active movement (TAM) evaluation system. In 5-FU group, the results were excellent in 22 fingers, good in 13 fingers, fair in 3 fingers and poor in 1 finger; the excellentand good rate was 89.7%. In control group, the results were excellent in 11 fingers, good in 15 fingers, fair in 9 fingers andpoor in 1 finger; the excellent and good rate was 72.2%. There was statistically significant difference in the functional recovery degrees of fingers between two groups (P lt; 0.05). The 2 fingers which had a poor result in 5-FU group and control group were served with tenolysis was performed in 2 cases having poor results after 6 months of operation and had an excellent result at last. Conclusion 5-FU appl ied topically can reduce tendon adhesions after the ruptured tendon repair.