Evaluation of local abciximab delivery from the surface of a polymer-coated covered stent: in vivo canine studies.

PURPOSE: To determine the in vitro feasibility of abciximab absorption and elution from a polymer-coated, silicone-covered stent, and to determine the in vivo effect of local delivery of abciximab concerning endothelialization of a polymer-coated, silicone-covered stent in a canine model. MATERIALS AND METHODS: Six polymer-coated, silicone-lined Wallstents were soaked in 2 mg/mL of concentrated solution of I131-labeled abciximab for a period as long as 48 hours. Quantification of abciximab absorption was determined by photon emission. Six maximally drug-loaded devices were then washed continuously with normal saline with use of a pustule pump apparatus. The quantity of residual abciximab was determined by photon emission for a period as long as 16 days. Eight similar devices (as described previously) were then implanted within the iliac arteries of four adult canines. Devices were identical except that four of eight were maximally loaded with abciximab. For each animal, one control implant was placed in the right iliac artery and one experimental implant (drug loaded) was placed in the left iliac artery, via right carotid cutdown. Animals were allowed to recover and no chronic medications were given. After an interval of 6 weeks, the animals were killed. Implants were isolated and perfused with 10% buffered formalin at a pressure of approximately 100 mm Hg for a period of 1 hour. Each implant was encased in methacrylate, sectioned into six equal segments, ground and polished, and stained with hematoxylin and eosin. Each slide was projected on a screen and the thickness of the neointima quantified. The mean neointima was determined for control and experimental groups, and compared for a potential significant difference with a Student t test. RESULTS: Mean absorption of abciximab was 21.53 microg +/- 2.99 per device. Devices were fully saturated at 24 hours. Forty percent was absorbed at 1 hour, and 60% and 80% were absorbed at 4 hours and 12 hours, respectively. Regarding elution, 30% of abciximab was washed out after 1 hour. There was a gradual elution of the drug to 16 days, with approximately 40% remaining at the end of the term. Mean neointimal thickness was 995 microm +/- 597 for the experimental group and 1,738 microm +/- 1,042 for the control group. The difference was significant (P <.05). CONCLUSIONS: Absorption and elution of abciximab from the surface of a covered stent is feasible. Local delivery of abciximab from the surface of this covered stent reduced the thickness of endothelial lining in the canine iliac artery compared to control.

Vascular stent prototype: in vivo swine studies.

PURPOSE: Evaluation of implantation technique and biocompatibility of a new balloon-expandable peripheral vascular stent. MATERIALS AND METHODS: Twenty-four stents, varying in diameter from 4 mm to 14 mm and length from 2 cm to 6 cm, were placed in eight microswine. After implantation, two of the animals were killed at 2 months and the remaining animals were killed at 6 months. All animals underwent premorbid angiography. The stents were then pressure fixed, harvested, and encased in methacrylate. The specimens were then sectioned by a diamond saw prior to staining. Individual specimens were then photographed, projected against a screen, and the neointimal thickness quantified by calibration with the diameter of the stent wire retained in the specimen. RESULTS: Technical success (implantation) was 96% (one embolization). All stents were widely patent at 2- and 6-month follow-up. Histopathologic examination demonstrated a very thin neointima covering the stent wires, with a maximum thickness measuring 254 microns. CONCLUSION: This new stent is safely implantable and biocompatible as tested in the arterial system of this animal model. Human clinical trials are indicated.

Prototype stent: in vivo swine studies in the biliary system.

PURPOSE: To evaluate the safety of implantation and the biocompatibility of a new balloon-expandable stent in the biliary system of the swine model. MATERIALS AND METHODS: Thirty stents, varying in diameter from 4 mm to 12 mm and in length from 2 cm to 6 cm, were placed in the bile ducts of 10 microswine. After implantation, one-third of the animal subjects were killed at 2 months and the rest, at 6 months. All animals underwent premorbid cholangiography. Stents were pressure fixed, harvested, and encased in methacrylate. Specimens were then sectioned with a diamond saw, prior to staining. Individual specimens were photographed for visualization of the histologic reaction. RESULTS: Technical success (implantation) was 100%. All stents were widely patent at 2-month and 6-month follow-up. Histopathologic study demonstrated a very thin epithelial hyperplasia that formed between stent wires. This did not cover the stent wires. CONCLUSION: This new stent is safely implantable and demonstrates minimal tissue reaction in the biliary system of the swine, when compared with other metallic biliary stents.

Use of polyetherurethane to improve the biocompatibility of vascular stents.

PURPOSE: To investigate potential differential growth on neointima following overdilating arterial trauma with polyetherurethane-coated versus bare metallic stents in swine. METHODS: Twelve specially constructed tantalum stents, 6 coated with polyetherurethane block copolymer and 6 uncoated, were overdilated by 25% in 12 normal renal arteries of six swine. The stents were harvested 8 weeks after implantation and prepared for histologic examination. Neointimal thickness was quantified and analyzed for significant differences between coated and uncoated prostheses. RESULTS: All specimens demonstrated fractures of the internal elastic lamina consistent with vascular injury. There was significantly less neointimal formation (0.0001 < p < 0.05) in coated specimens as compared to uncoated controls in each test animal. CONCLUSIONS: The vascular response to overdilating stent trauma appears to be moderated with the use of polyetherurethane block copolymer as compared to control.

Decreased platelet adherence of polymer-coated tantalum stents.

PURPOSE: To compare the acute thrombogenicity of polyurethane-coated stents with that of bare tantalum stents. MATERIALS AND METHODS: Thirty stents (15 coated with polyurethane) were balloon expanded in 8-mm x 80-cm sections of polytetrafluoroethylene grafts (six stents per graft). Under sterile conditions, 8- and 10-F vascular sheaths were placed percutaneously in the femoral artery and vein of a 100-lb (45-kg) swine. Platelets were labeled with indium-111 and reinjected for quantitative assay. The stented grafts were connected to the arterial and venous sheaths to create an ex vivo fistula. Each fistula was opened for 5, 10, 30, 60, or 120 minutes, exposing heparinized blood to fully expanded stents. The fistulas were closed, flushed with saline until clear, and fixed with formalin. Stents were explanted, placed in a radionuclide well counter, and scanned with electron microscopy. RESULTS: Quantitatively, there were considerably fewer platelets on coated versus uncoated stents. At 60 minutes, coated stents averaged 12.93 platelets per 1,000 microns 2 compared with 75.88 platelets per 1,000 microns 2 for bare metallic stents. At 120 minutes, there were 23.22 platelets/1,000 microns 2 versus 102.31 platelets/1,000 microns 2, respectively. Electron microscopy of coated stents demonstrated few scattered platelets at 5, 10, and 30 minutes. There was a uniform layer of platelets at 60 and 120 minutes. Uncoated stents demonstrated random areas of platelet clumping at 5, 10, and 30 minutes. At 60 and 120 minutes, uncoated stents showed extensive layering of platelets and fibrin. CONCLUSION: Polyurethane coating decreases platelet adhesion, relative to bare tantalum, at all time intervals tested.

Tantalum balloon-expandable stent: in vivo swine studies.

PURPOSE: The authors describe the experimental use of a balloon-expandable tantalum vascular stent in normal and atherosclerotic microswine. MATERIALS AND METHODS: Thirty-one stents (15 iliac, 13 aorta, two femoral, one renal) were placed in 11 animals. Stents were placed in both normal and stenotic atherosclerotic arteries. The animals were killed and the stents explanted 2-32 weeks after placement. Arteriography was performed just prior to death in all cases. RESULTS: All stents were patent arteriographically and on gross inspection. Histopathologic study showed a thin, smooth, endothelial-lined neointima over the segments with stents. This covering had a mean thickness of 2.9 x 10(-5) mm and appeared maximally developed 2-5 weeks after stent placement. The stent design incorporates the following engineering and clinical considerations: minimal profile and surface area and maximal expansion ratio, hoop strength, flexibility, fluoroscopic visibility, biocompatibility, and ease of placement. When compressed and mounted on the balloon catheter, the stent is flexible. This allows it to be easily maneuvered through tortuous or diseased vessels. On expansion, the stent becomes a semirigid tubular structure composed of multiple rhomboid cells. Stents with an expanded diameter of less than 11 mm can be introduced through a 7-F vascular sheath. CONCLUSION: Initial results suggest that this stent successfully incorporates a number of theoretically desirable features for a vascular prosthesis, and it may offer some advantages over previously described devices.