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Biomedical subjects

F O Tio

Publications and source records attributed to F O Tio.

At least 19 recordsLinked to original sources
PubMed2001

Effects of 32P radioactive stents on in-stent restenosis in a double stent injury model of the porcine coronary arteries.

BACKGROUND: The major limitation of coronary stenting remains in-stent restenosis, due to the development of neointimal proliferation. Radioactive stents have demonstrated the ability to reduce this proliferation in the healthy nonatherosclerotic porcine animal model. However, inhibition of tissue proliferation in the in-stent restenotic lesion in a porcine model is not well characterized. The objective of this study was to examine the efficacy and safety of the 32P radioactive stent for the treatment of in-stent restenosis in a double stent injury model of the porcine coronaries. METHODS AND MATERIALS: Eighteen coronary arteries in 9 pigs underwent nonradioactive stent (8 mm in length) implantation. Thirty days after the initial stent implantation, a 32P radioactive stent (18 mm in length) with an activity of 0 and 18 microCi was implanted to cover the initial stent. The swine were killed 30 days after the second stent implantation. Histomorphometric analysis was performed for vessel area (VA), stent strut area (SSA), intimal area (IA), and lumen area (LA). RESULTS: Injury scores, VA, SSA, and LA were similar among the control and radiated groups. Neointimal formation was significantly reduced after placement of radioactive stents as compared to control in both the overlapped (0.93 +/- 0.12 vs. 1.31 +/- 0.51 mm(2), p < 0.05) and nonoverlapped segments (1.14 +/- 0.21 vs. 1.91 +/- 1.04 mm(2), p < 0.05). The smooth muscle cell index in the neointima was reduced. Intimal fibrin was increased in the radiated group as compared to the control (p < 0.01 respectively). CONCLUSIONS: 32P radioactive stents may be safe and effective in reducing neointimal formation leading to in-stent restenosis. Longer follow-up will be required to examine whether these positive findings can be maintained.

Animals↗
PubMed2001

Failure of a novel balloon-expandable gamma-emitting ((103)Pd) stent to prevent edge effects.

BACKGROUND: Balloon-expandable beta-particle-emitting ((32)P) stents inhibit within-stent neointimal hyperplasia but induce lumen narrowing beyond the stent margins, ie, the so-called "edge effects." METHODS AND RESULTS: We prospectively investigated the performance of novel stents impregnated with the gamma-emitting isotope (103)Pd, designed to reduce edge effects, in 24 rabbits. The stents had a length of 18 mm and were mounted on 20-mm-long delivery balloons for deployment. Angiograms were obtained immediately and 1 month after direct implantation of control and 1-, 2-, and 4-mCi (103)Pd stents into the iliac arteries without predilatation or postdilatation. Late lumen loss was measured with quantitative angiography. Neointimal hyperplasia and vascular remodeling were evaluated by histomorphometry. Late lumen loss was inhibited within (103)Pd stents (control 0.18 mm, 1 mCi 0.08 mm, 2 mCi 0.05 mm, and 4 mCi -0.03 mm, P<0.05 all activities versus control). Conversely, late lumen loss occurred at the edges of (103)Pd stents, correlating with areas of high balloon/artery ratios and vessel overstretch injury. Edge effects were primarily due to neointimal hyperplasia but were also caused by negative vessel remodeling at high stent activities. CONCLUSIONS: Edge effects after implantation of radioisotope stents can occur independently of the isotope chosen for stent impregnation.

Angiography↗
PubMed2001

Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries.

BACKGROUND: The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited. METHODS AND RESULTS: A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. CONCLUSION: In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.

Angioplasty, Balloon↗
PubMed2001

Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia.

OBJECTIVES: We tested the hypothesis that intramyocardial injection of autologous bone marrow (ABM) promotes collateral development in ischemic porcine myocardium. We also defined, in vitro, whether bone marrow (BM) cells secrete vascular endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP-1). BACKGROUND: The natural processes leading to collateral development are extremely complex, requiring multiple growth factors interacting in concert and in sequence. Because optimal angiogenesis may, therefore, require multiple angiogenic factors, we thought that injection of BM, which contains cells that secrete numerous angiogenic factors, might provide optimal therapeutic angiogenesis. METHODS: Bone marrow was cultured four weeks in vitro. Conditioned medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic endothelial cells (PAEC) to assess proliferation. Four weeks after left circumflex ameroid implantation, freshly aspirated ABM (n = 7) or heparinized saline (n = 7) was injected transendocardially into the ischemic zone (0.2 ml/injection at 12 sites). Echocardiography to assess myocardial thickening and microspheres to assess perfusion were performed at rest and during stress. RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner. The conditioned medium enhanced, in a dose-related manner, PAEC proliferation. Collateral flow (ischemic/normal zone X 100) improved in ABM-treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0.001; 89 +/- 18 vs. 78 +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p = 0.49; 78 +/- 11 vs. 77 +/- 5 during adenosine, p = 0.75). Similarly, contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs. 60 +/- 32 at rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pacing, p = 0.056; controls: 69 +/- 48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p = 0.23). CONCLUSIONS: Bone marrow cells secrete angiogenic factors that induce endothelial cell proliferation and, when injected transendocardially, augment collateral perfusion and myocardial function in ischemic myocardium.

Animals↗
PubMed2000

Effect of percutaneous adenovirus-mediated Gax gene delivery to the arterial wall in double-injured atheromatous stented rabbit iliac arteries.

Though the efficacy of intravascular gene transfer has been demonstrated in native vessels following acute injury, this methodology has not been validated in complex models of vascular injury that more closely mimic clinical angioplasty procedures. Previous studies have shown that Gax gene overexpression modulates the injury-induced remodeling of the vessel in rat carotid and normal rabbit iliac arteries. Here, we evaluated the effect of the Gax gene delivery in atheromatous stented vessels. Rabbits were fed 120 g daily of 1% cholesterol diet for 3 weeks. At 1 week they underwent initial injury on the external iliac artery, then balloon angioplasty was performed at 3 weeks at the same site with a 2.5 mm diameter channel balloon catheter (three times 1 min at 6 atm). Either saline (n = 4) or the control viral construct Ad-CMVluc (5 x 109 p.f.u.) (n = 5) or Ad-CMVGax (5 x 10(9) p.f.u.) (n = 4) was delivered with a poloxamer mixture via a channel balloon (6 atm, 30 min), and a 15 mm long Palmaz-Schatz stent (PS154) was then deployed at the site (1 min, 8 atm). Arteries were analyzed 1 month later. At 1 month, the Ad-CMVGax treated arteries exhibited a lower maximal intimal area (1. 15+/-0.1 mm2) than saline (1.87+/-0.15 mm2, P = 0.007) or Ad-CMVluc-treated vessels (1.98+/-0.31 mm2, P = 0.04). Likewise Ad-CMVGax-treated vessels displayed a lower maximal percentage cross-sectional area narrowing (35.1+/-3.5%) than saline (65.3+/-9.4%, P = 0.01) or Ad-CMVluc-treated vessels (62.7+/-6.7%, P = 0.02). Angiographic analysis revealed larger minimal lumen diameter in Ad-CMVGax treated arteries (2.0+/-0.1 mm) than saline (1.14+/-0.36 mm, P = 0.06) or Ad-CMVluc-treated vessels (1.23+/-0.25 mm, P = 0.02). Overexpression of the Gax gene inhibits neointimal hyperplasia and lumen loss in atheromatous stented rabbit iliac arteries.

Adenoviridae↗
PubMed2000

Use of nitric-oxide-eluting polymer-coated coronary stents for prevention of restenosis in pigs.

BACKGROUND: Restenosis after angioplasty remains an unresolved problem despite an increase in use of coronary stents. It has been theorized that nitric oxide (NO) exerts several actions that can prevent restenosis. These include inhibition of proliferation of smooth muscle cells, prevention of arterial spasms, and decreasing aggregation of platelets in response to exposure to collagen. OBJECTIVE: To determine whether NO coated stents decrease restenosis in a pig balloon injury model. METHODS: We used coronary stents impregnated with a slow-release precursor of NO in the porcine model of restenosis. Tantalum coil coronary stents (Cordis) were coated with a polymer impregnated with a slow-release precursor of NO. Polymer-coated stents without active precursors were used as controls. Oversized stents were mounted on a delivery balloon and subsequently deployed in the right coronary and left anterior descending arteries of each animal. RESULTS: Repeated recording of angiograms demonstrated that changes in minimum lumen diameter on going from immediately after stenting to 28-day follow-up for the control and NO-eluting-stent groups were similar, namely decreases of 1.89 +/- 0.33 and 2.08 +/- 0.28 mm, respectively. The morphometric results, showing that severe luminal narrowing occurred for both groups, were similar. The percentage area stenoses were 85 +/- 5% for the control group and 84 +/- 6% for the NO-eluting group. Histology demonstrated that profuse formation of neointima and an inflammatory cell infiltrate occurred. CONCLUSIONS: Severe diameter stenosis occurred both for control and for treatment groups. The degree of angiographic stenosis was markedly worse than that previously reported for this model. Sustained release of a precursor of NO did not prevent restenosis in this model. This might have been due to a lack of efficacy of nitric oxide or to a profuse and overwhelming stimulatory effect of the polymer in the coated stents.

Angioplasty, Balloon, Coronary↗
PubMed1999

Evaluation of the acute and chronic safety of the biosense injection catheter system in porcine hearts.

Direct myocardial injection of therapeutic agents has been explored as a new method for myocardial revascularization. The integration of a 3D electromechanical mapping catheter with a retractable injection needle should allow for intramyocardial injection to identified sites, obviating the need for open heart surgery. This study assessed the procedural safety and performance characteristics of a novel guided catheter-based transendocardial injection system. The electromagnetic guidance system was coupled with a retrievable 27G needle for left ventricular endocardial injection. Using this system, we injected, transendocardially, methylene-blue (MB) dye tracer at a volume of 0.1 or 0.2 ml per injection in eight normal pigs. Animals were sacrificed acutely, at 1, 3, and 7 days (two animal in each time). Three animals served as controls. The injections were followed by coronary angiography and echocardiogram to assess possible ventricular or coronary perforation and wall motion abnormalities. CK-MB levels were measured up to 24 hr following the procedure. The animals were sacrificed at the assigned time for gross and histopathology evaluation. A total of 101 injections were made in all regions of the heart except the apex and the mitral valve. No animal died as a result of the mapping or injection procedures. Vital signs did not change relative to baseline after the mapping and injection procedures. CK-MB values did not increase over time and there was no evidence of sustained arrhythmia or hemodynamic compromise. There was no evidence of left ventricular or coronary perforation, global or regional wall motion abnormalities, or hemopericardium. On histologic evaluation, the estimated volume of tissue staining was greater than the volume of the injected MB dye due to dispersion of the injectate in the interstitial and intracellular fluid compartments. It is concluded that using this magnetic guidance catheter-based navigational system, it is feasible and safe to perform the transendocardial injection procedure. Thus, if it is determined that direct intramyocardial injection of drugs is a valid therapeutic strategy, this approach offers a clear advantage over surgically based transepicardial injection procedures. Cathet. Cardiovasc. Intervent. 48:447-453, 1999.

Animals↗
PubMed1999

Polytetrafluoroethylene-encapsulated stent-grafts: use in experimental abdominal aortic aneurysm.

PURPOSE: To evaluate expanded polytetrafluoroethylene (ePTFE) encapsulated stents for the treatment of aortic aneurysms with emphasis on the blood and tissue-material interactions. MATERIALS AND METHODS: Experimental aortic aneurysms were created in dogs by enlarging the aortic lumen with an abdominal fascial patch. Twenty animals underwent endoluminal repair after allowing the surgically created aneurysm to heal for 2 months prior to transluminal aneurysmal exclusion. The device used consisted of an 8-cm-long ePTFE encapsulated stent graft. The animals were killed in groups at 1 week and at 1, 2.25, 6, and 12 months. Specimens were processed for histologic and luminal surface studies. RESULTS: Before the animals were killed, aortography demonstrated two thrombosed aortae in the 6-month group and two endoleaks in the 12-month group. Endothelialized neointima extended into the proximal and distal portions of the prosthetic lumen, with minimal cell coverage in the center of the graft. The overall percent surface area covered by endothelialized neointima was 22% +/- 6% at 6 months and 18% +/- 10% by 1 year (P = .75). Histologic examination demonstrated minimal tissue penetration into the ePTFE. CONCLUSION: Transluminal exclusion of abdominal aortic aneurysms by encapsulated stent-graft is easily accomplished. With this device, tissue coverage and penetration of the stent graft is limited and does not tend to increase with time.

Animals↗
PubMed1999

Saline infusion via local drug delivery catheters is associated with increased neointimal hyperplasia in a porcine coronary in-stent restenosis model.

BACKGROUND: Catheter-based local drug delivery at the site of stent implantation has been proposed to reduce in-stent restenosis. We examined whether local delivery itself may cause additional vessel wall injury and negate the potential benefit of local drug delivery in a porcine coronary in-stent restenosis model. METHODS: Pigs were randomly assigned to no local delivery (controls, n = 10) or local saline infusion (5 ml) using commercially available catheters (n = 39; Dispatch catheter, Microporous Infusion catheter, and InfusaSleeve) prior to oversized (stent:artery ratio 1.2) coronary stent implantation. The amount of in-stent neointima was evaluated 4 weeks later with angiography and histology. RESULTS: There was no difference in vessel size or stent: artery ratio. However, at follow-up the local saline delivery group had significantly greater diameter stenosis (50 +/- 19% versus 25 +/- 17% in the controls, P < 0.01). Histology revealed similar injury scores but significantly greater neointimal area in the local saline group (3.61 +/- 1.11 mm2 versus 1.96 +/- 0.82 mm2 in the controls, P < 0.01). In a multivariate linear regression analysis, the use of the local delivery catheter was the only independent variable which was positively correlated with the amount of neointima (P = 0.0001). CONCLUSIONS: In this in-stent restenosis model, catheter-based local saline delivery was associated with significantly increased neointimal hyperplasia. Thus, for local drug delivery to reduce in-stent restenosis, the antiproliferative agent should be potent enough to compensate for the additional neointimal hyperplasia from the infusion itself.

Animals↗
PubMed1998

In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia.

OBJECTIVES: We examined the relative contributions of inflammation and arterial injury to neointimal formation in a porcine coronary overstretch restenosis model. BACKGROUND: Previous studies established that stents cause neointimal proliferation proportional to injury. Although inflammation has been postulated to be a major contributor to restenosis after angioplasty, there is a paucity of data on the relation between inflammation and subsequent neointimal formation. METHODS: Twenty-one pigs underwent balloon injury followed by implantation of oversized, tubular, slotted stents (stent/artery ratio 1.2:1) in the left anterior descending coronary artery. Morphometric analysis of the extent of injury (graded as injury score 0 to 3) and inflammation (graded as inflammation score 0 to 3) 1 month later was assessed and correlated with neointimal formation. RESULTS: An inflammatory reaction was observed in 20 of 21 pigs, and significant positive correlations were found between the degree of arterial injury and the extent of the inflammatory reaction (r = 0.80, p < 0.01) and between the extent of inflammatory reaction and the neointimal thickness (r = 0.75, p < 0.01), neointimal area (r = 0.53, p = 0.01) and percent area stenosis (r = 0.66, p < 0.01) within the stents. Importantly, there were areas with inflammation only in the absence of injury, and vice versa, that were also associated with neointimal hyperplasia. CONCLUSIONS: These data suggest that the inflammatory reaction plays an equally important role as arterial injury in neointimal formation after coronary stenting, and that anti-inflammatory approaches may be of value to reduce in-stent restenosis.

Animals↗
PubMed1998

Validation of the in vivo intravascular ultrasound measurement of in-stent neointimal hyperplasia volumes.

OBJECTIVES: This study was undertaken to validate the in vivo intravascular ultrasound (IVUS) measurement of in-stent neointimal hyperplasia (IH) volumes. BACKGROUND: Because stents reduce restenosis compared to balloon angioplasty, stent use has increased significantly. As a result, in-stent restenosis is now an important clinical problem. Serial IVUS studies have shown that in-stent restenosis is secondary to intimal hyperplasia. To evaluate strategies to reduce in-stent restenosis, accurate measurement of in-stent neointimal tissue is important. METHODS: Using a porcine coronary artery model of in-stent restenosis, single Palmaz-Schatz stents were implanted into 16 animals with a stent:artery ratio of 1.3:1. Intravascular ultrasound imaging was performed at 1 month, immediately prior to animal sacrifice. In vivo IVUS and ex vivo histomorphometric measurements included stent, lumen and IH areas; IH volumes were calculated with Simpson's rule. RESULTS: Intravascular ultrasound measurements of IH (30.4+/-11.0 mm3) volumes correlated strongly with histomorphometric measurements (26.7+/-8.5 mm3, r=0.965, p < 0.0001). The difference between the IVUS and the histomorphometric measurements of IVUS volume was 4.1+/-2.7 mm3 or 15.8+/-11% (standard error of the estimate=0.7). Both histomorphometry and IVUS showed that IH was concentric and uniformly distributed over the length of the stent. Intravascular ultrasound detected neointimal thickening of < or =0.2 mm in 5 of 16 stents. Sample size calculations based on the IVUS measurement of IH volumes showed that 12 stented lesions/arm would be required to show a 50% reduction in IVUS-measured IH volume and 44 stented lesions/arm would be required to show a 25% reduction in IH volume. CONCLUSION: In vivo IVUS measurement of IH volumes correlated strongly with ex vivo histomorphometry. Using volumetric IVUS end points, small sample sizes should be necessary to demonstrate effectiveness of strategies to reduce in-stent restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1997

Accelerated endothelialization by local delivery of recombinant human vascular endothelial growth factor reduces in-stent intimal formation.

Endothelium plays an important role in vascular smooth muscle cell proliferation and thrombus deposition. We thus hypothesized that local delivery of recombinant human vascular endothelial growth factor (rhVEGF) might reduce in-stent intimal formation. Balloon injury followed by Palmaz-Schatz stent implantation was performed in the external iliac artery of 30 New Zealand rabbits. Animals were then randomized to: 1) no local delivery (Control group, n=10); 2) local delivery via a channel balloon catheter of 100 microg rhVEGF165 (VEGF group, n=10); or 3) local delivery of the vehicle solution (Vehicle group, n=10). Animals were sacrificed 28 days later and morphometric analysis was performed. Maximal intimal area was reduced from 1.47+/-0.12 mm2 and 1.44+/-0.10 mm2 in the Control and Vehicle groups, respectively, to 0.87+/-0.06 mm2 in the VEGF group (p<.001). Accelerated endothelialization by local delivery of an endothelial-specific growth factor, rhVEGF, significantly reduces in-stent intimal formation and could constitute an attractive alternative to direct antiproliferative strategies.

Animals↗
PubMed1997

ACE inhibition accelerates endothelial regrowth in vivo: a possible explanation for the benefit observed with ACE inhibitors following arterial injury.

Recent in vitro studies suggest that angiotensin converting enzyme (ACE) inhibitors stimulate endothelial cell proliferation and migration. The present study was designed to test the hypothesis that an ACE inhibitor may accelerate endothelial regrowth in vivo. Twenty eight New Zealand White rabbits were randomized to receive placebo or the ACE inhibitor perindopril and underwent iliac balloon denudation. Endothelial regrowth, quantified 28 days after injury using Evans blue, was significantly greater in perindopril-treated animals than in controls (131 +/- 9 mm2 vs 69 +/- 8 mm2; P < .001). These results were confirmed by scanning electron microscopy and by specific immunostaining for endothelial cells. These data provide the first in vivo demonstration that ACE inhibitors accelerate endothelial regrowth after arterial injury. This effect may contribute to the benefit observed with ACE inhibition following arterial injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Stent endothelialization. Time course, impact of local catheter delivery, feasibility of recombinant protein administration, and response to cytokine expedition.

BACKGROUND: Because prior studies have established the critical role of the endothelium in preventing vascular thrombosis and intimal thickening, we designed a series of experiments to determine the feasibility of percutaneous local catheter delivery of recombinant protein to accelerate development of an intact endothelial monolayer after stent implantation. METHODS AND RESULTS: Balloon injury followed by percutaneous delivery of a 15-mm-long, balloon-expandable metallic stent was performed in 64 rabbit external iliac arteries (baseline diameter, 2.67 +/- 0.07 mm). Planimetric time-course analysis disclosed < 20% stent endothelialization at 4 days, < 40% at 7 days, and near-complete endothelialization at 28 days. The reporter protein horseradish peroxidase and the endothelial cell-specific recombinant protein vascular endothelial growth factor (VEGF) were each effectively delivered from a local delivery catheter (channel balloon catheter, ChB) after stent implantation. Although local catheter delivery (of vehicle control) itself mildly retarded the extent of stent endothelialization (10.6 +/- 2.9%) versus no local delivery (25.5 +/- 6.6%, P = .045), local ChB delivery of 100 micrograms VEGF overcame this catheter effect: By day 7, stent endothelialization was nearly complete (91.8 +/- 3.8%) (P < .0001 versus no local delivery). Consequently, stent thrombus was reduced in the VEGF-treated group (mural thrombus, 5.3 +/- 3.7%) versus no local delivery (29.3 +/- 6.8%, P = .006). Occlusive thrombus was seen only in the absence of local VEGF administration. CONCLUSIONS: (1) Local delivery of recombinant protein to the arterial wall is feasible after stent implantation, and (2) local delivery of the endothelial cell mitogen VEGF accelerates stent endothelialization, reducing stent thrombosis. These results thus establish a novel means by which the safety and/or bioactivity of endovascular stents may be further enhanced.

Angiography↗
PubMed1997

Continuous subcutaneous angiopeptin treatment significantly reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model.

BACKGROUND: In-stent restenosis results primarily from neointimal hyperplasia. This study evaluated the efficacy and the optimal mode of administration of angiopeptin, a somatostatin analogue with antiproliferative activity, in a porcine coronary in-stent restenosis model. METHODS AND RESULTS: Forty pigs were randomly assigned to one of four groups (n = 10 per group): (1) controls receiving saline infusion at the site of stent implantation via a local delivery catheter, (2) local treatment group receiving one-time treatment (200 (micrograms angiopeptin) at the site of stent placement, (3) systemic treatment group receiving continuous angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) and (4) combined local and systemic treatment group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery diameters, 1.3:1) was implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal percent diameter stenosis), intravascular ultrasound (total in-stent neointimal volume), and histology (maximal area stenosis). Systemic treatment produced the least neointimal hyperplasia and significantly reduced in-stent restenosis compared with the control group by all end points, despite similar degrees of injury. Angiography showed 25 +/- 17% versus 50 +/- 17% diameter stenosis in the systemic angiopeptin group versus the control group (P < .0001), intravascular ultrasound revealed 23 +/- 10 versus 58 +/- 27 mm3 neointimal volume in the systemic angiopeptin versus control group (P = .0002), and histology showed 41 +/- 16% versus 69 +/- 18% area stenosis (P = .0016) in the systemic angiopeptin versus control group. Plasma angiopeptin levels revealed rapid clearance (within 6 hours) after local therapy, whereas the levels persisted for up to 2 weeks in the systemic group. CONCLUSIONS: This study shows that continuous subcutaneous treatment with angiopeptin after stent implantation significantly reduces in-stent restenosis by inhibiting neointimal hyperplasia.

Animals↗
PubMed1997

Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening.

OBJECTIVES: This study sought to test the hypothesis that direct gene transfer of an endothelial cell mitogen could passivate metallic stents by accelerating endothelialization of the prosthesis. BACKGROUND: Thrombosis and restenosis comprise the principal clinical manifestations of compromised biocompatibility of endovascular stents. Previous studies have demonstrated that endothelial recovery at sites of balloon injury is a critical determinant of consequent intimal thickening and mural thrombus. We therefore investigated the potential for an endothelial cell mitogen delivered as plasmid DNA to optimize stent biocompatibility. METHODS: Naked plasmid DNA encoding vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) (phVEGF165) was delivered locally using a hydrogel-coated balloon angioplasty catheter to 16 rabbit iliac arteries in which metallic stents had been placed at the site of balloon injury; the contralateral iliac artery of each rabbit was balloon injured and stented but not transfected. RESULTS: Stent endothelialization was accelerated by phVEGF165 gene transfer (87.38 +/- 5.06% vs. 33.13 +/- 9.73% [mean +/- SEM] of the planimetered stent surface in the treated vs. contralateral limb, p = 0.005). This was associated with a significant reduction in mural thrombus (3.7 +/- 2.4% vs. 32.7 +/- 9.7%, p = 0.01) at day 7 and intimal thickening (maximal intimal area 0.61 +/- 0.09 vs. 1.44 +/- 0.12 mm2, p < 0.0001) at day 28. No benefit was observed from pCMV-luciferase in 14 similarly instrumented control rabbits. CONCLUSIONS: These findings indicate that arterial gene transfer of naked plasmid DNA encoding for an endothelial cell mitogen may successfully passivate endovascular stents by accelerating stent endothelialization, thereby reducing in-stent thrombus and obstruction due to intimal thickening.

Angioplasty, Balloon↗
PubMed1997

Acute and chronic effects of self-expanding nitinol stents in porcine coronary arteries.

BACKGROUND: There is a paucity of experimental data regarding self-expanding stents. This study evaluated the acute and chronic effects of CardioCoil, a self-expanding nitinol coil stent, in porcine coronary arteries. METHODS: Twenty-three self-expanding nitinol stents were implanted without associated balloon angioplasty in normal coronary arteries of 12 pigs, which were serially sacrificed up to 6 months. Angiographic and histologic analyses were performed to evaluate the deployment characteristics, patency rates, neointimal response, and unique features of the self-expanding nature of the CardioCoil stent. RESULTS: All stents were successfully deployed and remained patent acutely. Three undersized stents migrated proximally and there was one episode of subacute thrombosis in an oversized stent. The remaining stents were patent throughout the survival period and neointimal responses were favorable for up to 6 months (all mean neointima < 200 microns up to 6 months). There was evidence of continuing stent expansion over time (stent diameter 2.85 +/- 0.78 mm immediately after deployment and 3.24 +/- 0.97 mm at follow-up) and the majority of stent struts were in the adventitia by 6 months. Re-endothelization occurred starting one week after implantation and was complete by 8 weeks. CONCLUSIONS: This study shows that the CardioCoil self-expanding nitinol coil stent, is associated with favorable deployment characteristics and patency rates, although appropriate sizing is more crucial than with balloon-expandable stents. More importantly, there appears to be a "dissociation' between the deep vessel wall injury by the chronic strut expansion process and the neointimal reaction, unlike balloon-expandable stents.

Alloys↗