In vivo comparison of a polymer-free Biolimus A9-eluting stent with a biodegradable polymer-based Biolimus A9 eluting stent and a bare metal stent in balloon denuded and radiated hypercholesterolemic rabbit iliac arteries.

OBJECTIVES: To evaluate the effect of a polymer-free Biolimus A9-eluting stent [BioFreedom (BF)], compared with that of a biodegradable polymer-based Biolimus A9-eluting stent [BioMatrix Flex (BMF)] and a bare metal stent (BMS) in balloon denuded and radiated hypercholesterolemic rabbit iliac arteries. METHODS: Rabbits were fed with 1% cholesterol diet (n = 14) for 14 days, both iliac arteries were balloon denuded and radiated, and then rabbits were switched to 0.15% cholesterol diet. After 4 weeks, BF (n = 8), BMF (n = 8), and BMS (n = 8) were deployed in denuded and radiated areas. Four weeks later animals were euthanized, arterial segments were processed for morphometry. RESULTS: The neointimal area in vessels implanted with BF stents was significantly less than that seen in vessels implanted with BMS (0.90 mm(2) ± 0.14 vs. 1.29 mm(2) ± 0.23, P <0.01). Percent fibrin and fibrin score were higher with BMF stents compared to BMS (P <0.03 and <0.04) and giant cell number was significantly higher with both BMF and BF stents (P < 0.01 for both). Percent endothelialization was significantly higher and % uncovered struts were lower with BMS compared to either BMF or BF stents (P < 0.05 for both). CONCLUSION: This study demonstrates that compared to BMS, BF stents significantly decreased neointimal hyperplasia.

Effects of exogenous peripheral-blood-derived endothelial progenitor cells or unfractionated bone-marrow-derived cells on neointimal formation and inflammation in cholesterol-fed, balloon-denuded, and radiated iliac arteries of inbred rabbits.

BACKGROUND: Injection of bone marrow cells (BMC) and endothelial progenitor cells (EPC) or application of stem-cell-mobilizing factors has been associated both with reduction or exacerbation of atherosclerosis and with unstable plaque phenotype. The discrepancies may reflect the cell type, dosing, duration, and route of administration of cells in these studies. The aim of this study was to determine the effects of peripheral-blood-derived endothelial progenitor cells (PBEPC) or unfractionated BMC obtained from inbred siblings on neointimal formation and inflammation in cholesterol-fed, balloon-denuded, and radiated rabbit iliac arteries. METHODS: Rabbits were fed a 1.0% cholesterol diet for 14 days, followed by endothelial denudation in both iliac arteries, and continued on a 0.15% cholesterol diet. On day 42, denuded areas were radiated, and animals were randomized. The first group received PBEPC (n=5), the second group received BMC (n=4), and the third group received heparinized (20 IU) saline (Control; n=3). PBEPC were characterized by flow cytometry. Cells (5x10(6)) or saline was administered twice through the ear vein: the first time at 1 h after radiation and the second time at 2 weeks after radiation. Four weeks after radiation, the animals were sacrificed, and arterial segments were processed for morphometry. RESULTS: Administration of BMC or PBEPC from inbred siblings had no adverse effect. Lumen area (0.93+/-0.53 mm(2)), neointimal area (0.65+/-0.29 mm(2)), percent stenosis (44+/-21), and macrophage score (0.6+/-0.3) in controls were similar to those in cell-treated groups. CONCLUSION: This study demonstrates that, in the current animal model, either PBEPC or BMC failed to affect neointimal formation or inflammation.

PhotoPoint photodynamic therapy promotes stabilization of atherosclerotic plaques and inhibits plaque progression.

OBJECTIVES: The purpose of this study was to determine how photodynamic therapy (PDT) promotes stabilization and reduction of regional atherosclerosis. BACKGROUND: Photodynamic therapy, a combination of photosensitizer and targeted light to promote cell apoptosis, has been shown to reduce atherosclerotic plaque inflammation. METHODS: Forty New Zealand White rabbits were fed with cholesterol. The iliac arteries were balloon denuded and randomized to receive either PhotoPoint PDT treatment (photosensitizer and light) (Miravant Medical Technologies, Santa Barbara, California), photosensitizer (MV0611) alone, or light alone and were then compared at 7 and 28 days. Arteries were examined for evidence of plaque volume, cell number, macrophage and smooth muscle cell (SMC) content, and plaque cell proliferation. RESULTS: Compared with contralateral iliac artery controls at 7 days, plaque progression was reduced by approximately 35% (p < 0.01); plaque progression was further reduced to approximately 53% (p < 0.01) by 28 days, leading to an increase in lumen patency (p < 0.05). At 7 days after PDT, percent plaque area occupied by macrophages decreased by approximately 98% (p < 0.001) and SMCs by approximately 72% (p < 0.05). At 28 days after PDT, removal of macrophages was sustained (approximately 92% decrease, p < 0.001) and plaques were repopulated with non-proliferating SMCs (approximately 220% increase, p < 0.001). There was no evidence of negative or expansive arterial remodeling, thrombosis, or aneurysm formation. CONCLUSIONS: Photodynamic therapy simultaneously reduces plaque inflammation and promotes repopulation of plaques with a SMC-rich stable plaque cell phenotype while reducing disease progression. These early healing responses suggest that PDT is a promising therapy for the treatment of acute coronary syndromes.

Effect of clopidogrel on neointimal formation and inflammation in balloon-denuded and radiated hypercholesterolemic rabbit iliac arteries.

BACKGROUND: Platelet-derived peptide and nonpeptide growth factors are known to play pivotal roles in neointimal proliferation. Along with its antiplatelet activity of reducing P-selectin and hs-CRP, clopidogrel has also been shown to have anti-inflammatory properties. The aim of this study is to find out by modulating inflammation if clopidogrel can affect neointima formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits. METHODS AND RESULTS: Rabbits were fed with 1% cholesterol diet with (n = 20) or without (n = 20) clopidogrel (10 mg/kg body weight) for 7 days followed by balloon-denudation of endothelial layer in both the iliac arteries and continued on 0.15% cholesterol diet with or without clopidogrel. Four weeks later, the denuded area in both iliac arteries was radiated (n = 11, cholesterol-only group; n = 9, clopidogrel group) or sham treated (n = 10 from each group). Four weeks after radiation, animals were sacrificed and arterial segments were processed for morphometry. In the sham-treated clopidogrel group, neointimal area, percent stenosis, and macrophage score were 39% (P = 0.01), 32% (P = 0.02), and 50% (P = 0.02) smaller, respectively, when compared to the cholesterol-only group (0.48 +/- 0.18, 32.42 +/- 13.04, and 1.5 +/- 0.83). There were no differences in the radiated group (0.89 +/- 0.32, 50.34 +/- 13.00, and 1.88 +/- 1.27 vs. 0.93 +/- 0.38, 59.41 +/- 11.41, and 2.00 +/- 0.74, respectively). CONCLUSION: This study demonstrates that clopidogrel reduces inflammation and neointimal formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits.

Short-term effects of biocorrodible iron stents in porcine coronary arteries.

BACKGROUND: Biocorrodible iron stents carry the potential to overcome limitations, such as chronic inflammation and premature recoil, posed by biodegradable polymer and magnesium alloy stents. This study aimed to test the safety and efficacy of biocorrodible iron stents in porcine coronary arteries. METHODS: Iron stents and cobalt chromium stents were randomly deployed in the coronary arteries of juvenile domestic pigs. Animals were sacrificed at 28 days, and the vessels were fixed and processed for histochemistry. RESULTS: At 28 days, iron stents started to show signs of degradation without evidence of stent particle embolization or thrombosis without traces of excess inflammation, or fibrin deposition. At 28 days, the surface of the iron stent struts was black to brown and the vascular wall adjacent to the iron stent had a brownish tinge. There were no statistically significant differences in any of the measured parameters between segments implanted with iron and cobalt chromium stents. There were also no adverse effects in the persistent areas. CONCLUSION: The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents.

Efficacy and safety of pimecrolimus-eluting stents in porcine coronary arteries.

OBJECTIVE: We aimed to evaluate an effective dosage and safety profile of pimecrolimus as an anti-inflammatory drug for drug-eluting stents. METHODS: In the dose finding study, coronary arteries of 20 domestic swine were randomly implanted with bare metal stents (ProKinetic and Guidant Vision), the ProKinetic stent with polylactic acid (PLLA), and pimecrolimus-eluting stents (32, 75, and 120 microg) over a period of 4 weeks. In addition, pimecrolimus (75 microg) and ProKinetic stents were randomly implanted into six swine over 3 months. In the safety study, the ProKinetic stent, the ProKinetic stent with PLLA, mid- (45 microg) and high-dose pimecrolimus (120 microg), and overlapping mid-dose stents were implanted over a period of 4 weeks. Mid-dose, ProKinetic stent, and ProKinetic stent with PLLA were implanted over a period of 3 months. RESULTS: The dose finding study revealed excellent luminal patency with low percent occlusion (approximately 29% vs. approximately 41%), injury (0.53-0.59 vs. 1.25), and inflammation (0.78-0.97 vs. 1.08) for the pimecrolimus group compared with the vision group. The safety study arm showed similar angiographic results for all tested groups, with a significantly larger minimal lumen diameter for pimecrolimus stents compared to PLLA stents. Except for the high-dose group and overlapping area of the overlapping group, promising morphometric results were found for pimecrolimus compared to bare metal stents. CONCLUSIONS: Present data suggest that pimecrolimus-eluting stents are safe and have a similar healing profile to bare metal stents. They may suppress inflammation, leading to a reduced intimal response and a milder inflammatory reaction in a porcine model.

Safety and efficacy of bioabsorbable magnesium alloy stents in porcine coronary arteries.

OBJECTIVE: We aimed to determine the safety and efficacy of biobasorbable magnesium alloy stents in porcine coronary arteries. Bioabsorbable magnesium stents carry the potential to overcome the limitations posed by permanent metallic stents such as chronic inflammation, late stent thrombosis, prolonged antiplatelet therapy, and artifacts when imaged by multislice-computed tomography or magnetic resonance imaging. METHODS: Magnesium alloy stents or stainless steel stents were randomly deployed in coronary arteries of domestic or minipigs. Domestic pigs were sacrificed at 3 days (n = 2) or 28 days, and minipigs at 3 months. RESULTS: At 3 days, magnesium alloy stents were intact, but started to show signs of degradation by 28 days. There was no evidence of stent particle embolization, thrombosis, excess inflammation, or fibrin deposition. At 28 days and 3 months, neointimal area was significantly less in magnesium alloy stent segments (2.44 +/- 0.88 mm(2) and 1.16 +/- 0.19 mm(2)) as compared with the stainless steel stent segments (5.03 +/- 1.5 mm(2) and 1.72 +/- 0.68 mm(2), P < 0.001 and 0.02). Quantitative coronary analysis indicates that percentage area stenosis and percentage diameter stenosis in magnesium alloy stent segments improved significantly at 3 months as compared to 28 days. Despite decreased neointimal hyperplasia, lumen area of the magnesium alloy stented vessels did not improve significantly. CONCLUSION: Magnesium alloy stents are safe and are associated with less neointima formation; however, reduced neointima did not result in larger lumen.

Optimal dosing and duration of oral everolimus to inhibit in-stent neointimal growth in rabbit iliac arteries.

BACKGROUND: Everolimus is an orally active derivative of sirolimus. Oral administration of rapamycin is efficacious in the reduction of neointima formation and clinical restenosis; however, its optimal dose and duration have not been determined. METHODS: New Zealand White rabbits were divided into three groups. The first (low-dose) group received 1.5 mg/kg everolimus 1 day before stenting, followed by 0.75 mg/kg/day everolimus for 28 days. The second (high-dose) group received 6 mg/kg everolimus 1 day before, on the day of, and on the day after stenting, followed by 2 mg/kg/day for 4 days. The third (placebo) group received a matching volume of vehicle similar to that of Group 2. Twenty-eight days after stenting, animals were euthanized and morphometry was performed. RESULTS: In the high-dose group, circulating everolimus levels corresponded with administrated dose levels; by Day 12, no circulating everolimus could be detected. In the low-dose everolimus group, levels remained constant up to 28 days. When compared with placebo, low-dose everolimus was associated with a significant reduction in medial thickness (32%), neointimal area (60%), and percent stent stenosis (33%); however, high-dose everolimus had no significant effect. CONCLUSIONS: In conclusion, oral everolimus suppresses in-stent neointimal growth in rabbit iliac arteries. Four weeks of low-dose everolimus is more effective than 7 days of high-dose everolimus.

Peroxisome proliferator-activated receptor gamma ligand pioglitazone alters neointimal composition in a balloon-denuded and radiated hypercholesterolemic rabbit.

Peroxisome proliferator-activated receptor (PPAR)-gamma activation suppresses inflammatory response, monocyte recruitment, and vascular cell proliferation. Because inflammation, deregulated growth, and migration of monocytes and vascular smooth muscle cells (VSMC) play important roles in the development of neointima, we tested the effect of pioglitazone, a high-affinity ligand, for PPAR-gamma on neointima formation in the iliac arteries of a balloon-denuded and radiated hypercholesterolemic rabbit. Rabbits were fed a 1.0% cholesterol diet for 7 days followed by denudation of endothelial layer and continued on a 0.15% cholesterol diet. On day 32, animals were divided into 2 groups. One group received a 0.15% cholesterol diet (n = 7) and the other group received a 0.15% cholesterol diet supplemented with 400 mg of pioglitazone per kilogram. On day 35, the balloon-denuded area was radiated. Four weeks after radiation, animals were sacrificed and arterial segments were processed for morphometry and immunohistochemistry. Data analysis showed that the pioglitazone group had smaller neointima (0.85 +/- 0.36 vs. 1.41 +/- 0.56, P < 0.05), with more cells positive for VSMC (23.07 +/- 6.16 vs. 18.33 +/- 5.19, P = 0.04), less for monocytes (16.01 +/- 5.33 vs. 21.29 +/- 4.33, P < 0.05), and fewer cells expressing metalloproteinase (MMP)-1 and MMP-9 (3.69 +/- 0.47 vs. 4.82 +/- 0.93, P < 0.05 and 3.24 +/- 0.71 vs. 4.29 +/- 0.74, P < 0.05, respectively). Pioglitazone reduced neointimal area and modified its composition in a balloon-denuded and radiated hypercholesterolemic rabbit model.

Effect of antioxidants on atherosclerotic plaque formation in balloon-denuded and irradiated hypercholesterolemic rabbits.

The oxidative modification of low-density lipoprotein (LDL) hypothesis implies that antioxidants should be effective in suppressing atherosclerosis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and irradiated hypercholesterolemic rabbits. Rabbits were fed with a 1% cholesterol diet supplemented with or without a mixture of antioxidants (vitamin E, vitamin C, selenium, zinc, copper, manganese, N-acetylcysteine, glutamine). At 7 days both iliac arteries were balloon denuded, and 4 weeks later, 1 iliac artery underwent endovascular irradiation (n=12), while the contralateral was sham treated (n=12). Four weeks after irradiation, animals were euthanized, and arteries were fixed and processed for histo- or immunohistochemistry for determining the plaque area, macrophage count, and oxidized LDL-positive areas. Plasma antioxidant levels were significantly higher in the animals fed with antioxidant diet. Plasma (thiobarbituric acid-reactive substances) and arterial tissue oxidized LDL (immunoreactive to specific oxidized LDL antibody) levels were significantly higher in the irradiated as compared with nonirradiated animals (0.69+/-0.09 and 31.05+/-4.21 versus 0.24+/-0.04 and 18.42+/-4.62, P<0.001 and 0.05), and antioxidants partially lowered the oxidized LDL levels (0.35+/-0.14 and 25.41+/-4.82, P<0.001 and 0.01). Plaque area in the irradiated animals was 175% greater than in nonirradiated animals (P<0.05). Antioxidant supplementation resulted in a 50% decrease in plaque area of both control and irradiated animals. Antioxidants reduced both the cholesterol-induced and radiation-enhanced circulating and tissue oxidized LDL levels, resulting in reduced plaque.

Novel site-specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model.

Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC-based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 +/- 0.84 vs. 4.77 +/- 1.71 mm2, respectively; P < 0.001). In the porcine coronary model, site-specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments.

Effects of contrast media on porcine bone marrow-derived mononuclear cells and calf myoblast viability and secretion of VEGF and MCP-1.

We investigated the effect of contrast media on bone marrow-derived cell viability, growth factor secretion, and myoblast viability. Bone marrow was exposed to contrast media, mononuclear cells were isolated, viability was assessed by Trypan blue exclusion or cultured for 4 weeks, and conditioned medium was assayed for vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1). Skeletal myoblasts viability was assessed after exposing them to contrast media. In separate experiments, bone marrow or bone marrow-derived mononuclear cells were exposed to contrast media, cultured for 40 hr, then assessed for viability. None of the contrast media tested had any effect on bone marrow-derived cell viability. Hypaque or Hexabrix increased myoblasts viability by 8-10%. VEGF and MCP-1 concentrations in the conditioned medium increased in a time-related manner. These findings support the concept that for cell therapy, bone marrow cells or myoblasts may be mixed with contrast media and injected into ischemic myocardium without compromise in viability or function.

Effect of ionizing radiation on the stability and performance of the TAXUS Express2 paclitaxel-eluting stent.

BACKGROUND: The advent of drug-eluting stents has provided the interventional cardiologist an effective new tool in treating coronary restenosis. There remains, however, a small group of patients that still require intervention following drug-eluting stent therapy. Currently, intravascular brachytherapy (IVBT) is approved for use in the treatment of in-stent restenosis (ISR). This study investigated the effect of gamma and beta radiation doses typically used in IVBT on the performance of the TAXUS Express(2) paclitaxel-eluting stent. METHODS AND RESULTS: It was determined that there were no statistically significant changes to in vitro paclitaxel release from stent exposed to radiation compared to controls subjected to the same conditions except for the radiation exposure. The molecular weight of the Translute polymer carrier matrix and the level of paclitaxel degradants were not changed following exposure to radiation doses up to twice what is typically used in IVBT. Beta and gamma radiation doses typically used in IVBT had no significant effect on the Translute polymer carrier, paclitaxel degradation, or paclitaxel release in this in vitro model. CONCLUSION: The data are encouraging and support further evaluation of the use of IVBT in the treatment of ISR in the presence of drug-eluting stents.

Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium.

OBJECTIVE: Cell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart. METHODS: Myocardial infarction was produced in 13 domestic swine. At 4 weeks, animals were randomized to receive transepicardial injections of autologous BMMNCs (approximately 24x10(6) cells, n=8) or phosphate buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral growth, angiogenesis, and infarct size were assessed by angiography, immunohistochemistry, and histomorphometry. RESULTS: Regional contractility was assessed by transepicardial echocardiography at baseline and 4 weeks following treatment. Angiography revealed a trend toward increased collateral growth in the BMMNC group. Wall motion score index (myocardial function) was similar in both groups at baseline (1.63+/-0.16 vs. 1.25+/-0.25, P=.21) and at 4 weeks (1.83+/-0.22 vs. 1.63+/-0.38, P=.62). alpha-Actin-positive smooth muscle cells (SMCs) and Factor VIII positive endothelial cells were significantly greater in the BMMNC-injected animals (314.8+/-37.4/0.1 vs. 167.1+/-11.9/0.1 mm(2) in controls, P=.02, and 363.3+/-28.2 cells/0.1 mm(2) vs. 254.4+/-28.1 cells/0.1 mm(2) in controls, P=.03, respectively). The number of blood vessels >50 mum in diameter was significantly increased in the BMMNC group (317.9+/-54.9 vs. 149.1+/-6.1, P<.05). The size of the infarct area was smaller in the BMMNC-transplanted group than in the controls (P=.015). CONCLUSION: BMMNC transplantation appears to improve angiogenesis and reduce infarct size yet results in no improvement in left ventricular function in a chronically infarcted heart.

Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model.

HYPOTHESIS: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. METHODS: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. RESULTS: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63+/-1.99 vs. 4.77+/-.1.71 mm2, respectively, P<.05). CONCLUSION: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.

Effectiveness of radioactive tungsten source in the prevention of restenosis in stented porcine coronary arteries.

PURPOSE: Intracoronary radiation has shown the potential to inhibit neointimal proliferation in porcine models of restenosis. The objective of this study was to determine whether intracoronary radiation using a new coiled wire of tungsten-188 ((188)W), a pure beta emitter (half-life 69.4 days) is safe. In addition, a dose of 0 Gy, 18 Gy, or 25 Gy prescribed to 2 mm from the center of the source and delivered intraluminally is sufficient to prevent restenosis and free from adverse effects. METHODS AND MATERIALS: Ten domestic swine underwent 13-mm stent implantation (SI) into two arteries, left anterior descending plus either the left circumflex or right coronary artery. After SI, a closed-end lumen radiation catheter was inserted to the treated artery and a 40-mm coiled (188)W source was manually delivered to cover the stented segment and its margins. A total of 20 arteries were randomized to treatment with a radiation dose of 0, 18 Gy, or 25 Gy delivered to 2 mm depth from the center of the source. Four weeks after the procedure, the swine underwent angiography and intravascular ultrasound using automated pullback at 0.5 mm/s. before being killed and the arteries perfusion fixed. Histopathologic and histomorphometric analyses were performed at 28 days after injury and radiation. RESULTS: Irradiation with (188)W at a dose of 25 Gy after SI significantly inhibited neointima formation (intimal area: 1.05 +/- 0.64 vs. 2.75 +/- 0.99 mm(2), p < 0.01) and at an 18 Gy dose of radiation (intimal area: 1.73 +/- 0.49 vs. 2.75 +/- 0.99 mm(2)), as compared to controls. One artery receiving 18 Gy and two arteries receiving 25 Gy were totally occluded at follow-up due to thrombus formation but no edge stenosis was observed in any of the irradiated arteries. CONCLUSIONS: Intracoronary radiation therapy using a new coiled wire of (188)W source delivered after SI appeared to be safe and well tolerated. The radiation doses demonstrated efficacy in reducing neointima formation in the porcine coronary stent injury model.