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.

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.

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.

Re-expansion of balloon-expandable stents after growth.

OBJECTIVES: The purpose of this study was to evaluate the feasibility of re-expansion of balloon expandable intravascular stents and to examine the gross and histologic effects of re-expansion on vascular integrity. BACKGROUND: Intravascular stents have been used successfully as an adjunct to balloon dilation of congenital pulmonary artery branch stenosis and postoperative stenosis of the pulmonary arteries in children. However, use of rigid stents in children could result in development of relative stenosis at the site of stent implantation with subsequent growth of the child. METHODS: Stainless steel "iliac" stents were placed in the thoracic aorta of 10 normal juvenile swine by a transcatheter technique. Angiography and re-expansion were performed at a mean of 11 weeks (n = 9) and again at 18 weeks (n = 5). After euthanasia, the aortic specimens were removed for gross and histologic examination. RESULTS: Stents were successfully implanted in 10 swine. Re-expansion was successfully performed in each animal at 11 weeks and at 18 weeks. Aortic growth produced a relative constriction of the aorta of 20% +/- 10% (mean +/- SD) at the site of stent implantation at both 11 and 18 weeks. Re-expansion produced a significant increase in mean stent diameter from 10.1 +/- 1 mm to 12.3 +/- 1.2 mm at 11 weeks and from 11.2 +/- 0.7 to 13.5 +/- 1.1 mm at 18 weeks after implantation (p < 0.001). Balloon dilation produced a relative increase in stent diameter of 21% +/- 7% at 11 weeks and 18% +/- 4% at 18 weeks. Stent re-expansion was accompanied by plastic deformation of the neointima without neointimal dissection. Where neointima was thick, there was no evidence of neointimal abrasion, but where neointima was thin, areas of localized neointimal abrasion were observed with focal fibrin and platelet adherence to the stent struts. There was no evidence of medial or adventitial hemorrhage or dissection produced by re-expansion. CONCLUSIONS: Re-expansion of intravascular stents is feasible after growth in juvenile swine without significant injury to neointima, media or adventitia. The results of this study support careful and selective use of intravascular stents as an adjunct to balloon dilation of congenital stenoses in children.

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.

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.

Interleukin-2 receptor-specific fusion toxin inhibits barotrauma-induced arterial atherosclerosis.

Immunocytochemical analyses of human plaques and experimental arterial lesions have implicated activated lymphocytes and monocytes in the pathogenesis of atherosclerosis, as demonstrated by the expression of interleukin-2 (IL-2) membrane receptors and major histocompatibility complex class II epitopes. The objective is to determine if targeting these cells with an IL-2 receptor-specific chimeric toxin, DAB486-IL-2, can inhibit experimental post-angioplasty vascular neointimal thickening. Twenty-two atherogenically modeled rabbits were treated in vivo with DAB486-IL-2 (0.1 mg/kg per day i.v.; n = 11) or placebo (n = 11) for 10 days following aortic balloon angioplasty (4 atm x 30 s each x 2 dilatations). In vitro 3H-leucine incorporation studies of mononuclear leukocyte and vascular smooth muscle cell protein synthesis inhibition by DAB486-IL-2 were also performed. Angioplasty sites were examined for evidence of hyperproliferative atherosclerotic narrowing by quantitative angiography and histomorphometry of neointimal cross-sectional area at baseline and 6 weeks after injury. In vitro Concanavalin-A stimulated rabbit mononuclear leukocyte protein synthesis was 50% inhibited by DAB486-IL-2 at a concentration (IC50) of 6 x 10(-11) M. Rabbit vascular smooth muscle cells were approximately 150-fold less sensitive to DAB486-IL-2 (IC50 = 10(-8) M). In vivo studies showed no change in angioplasty site angiographic minimum luminal diameter at 6 weeks in DAB486-IL-2 treated animals (from 2.96 +/- 0.52 to 2.96 +/- 0.48 mm; percent cross-sectional area reduction = 1 +/- 10%; P = N.S.). In control animals, luminal diameter decreased from 2.79 +/- 0.4 to 2.32 +/- 0.52 mm at 6 weeks, and percent cross-sectional area was reduced by 34 +/- 14% (P < 0.01 vs. placebo). Quantitative histomorphometric angioplasty segmental intimal cross-sectional area reduction of treated and placebo vessels also differed significantly (19 +/- 16% vs. 31 +/- 21%; P < 0.05). DAB486-IL-2 caused no adverse effects on animal survival, weight or hepatic transaminase levels. We conclude that post-angioplasty administration of the chimeric toxin DAB486-IL-2 inhibits angiographic narrowing and neointimal thickening in the atherogenic rabbit model. Although this IL-2 receptor-specific molecule was cytotoxic in vitro for activated mononuclear leukocytes and vascular smooth muscle cells, systemic toxicity did not occur in vivo at a dose comparable to that evaluated in clinical trials of this agent. Potential anti-proliferative effects of this chimeric toxin may be mediated by direct local inhibition of leukocyte-mediated inflammation, or through the indirect modification of vascular cell mitogenesis and cytokine release.

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.

Black thyroid syndrome: exaggeration of a normal process?

Coal-black thyroid discoloration usually is identified in patients receiving chronic minocycline therapy. This report concerns the use of light microscopic, electron microscopic, and energy dispersion spectroscopy of thyroid pigments in three separate situations: minocycline-associated black thyroid; idiopathic black thyroid; and normally pigmented thyroid glands. One of the pigments, which is found in each situation, is best described as neuromelanin. This melanin pigment, like lipofuscin, appears to accumulate with advancing age. Pigment accumulation, therefore, is a normal process in the thyroid gland. Accelerated pigment accumulation occurs with minocycline therapy but can uncommonly be seen without associated minocycline treatment. Possible mechanisms for the development of these pigments in normal and black thyroid glands are discussed. Minocycline-associated pigment is also described in substantia nigra and atherosclerotic plaques.

Expandable intraluminal vascular graft: a feasibility study.

An expandable intraluminal graft mounted coaxially over an angioplasty balloon catheter was used in dog arteries. The graft, a wire mesh tube that has the ability to retain its expanded shape, opposes elastic recoil of the arterial wall after maximum balloon inflation. Eighteen grafts were placed in the abdominal aorta and iliac femoral, renal, superior mesenteric, and carotid arteries of eight dogs through femoral or carotid arteriotomies. Two grafts were placed in areas of artificially induced stenosis, completely restoring the lumen. Overall patency rate at 35 weeks was 77%. Histopathologic examination of patent grafts showed complete endothelialization at 3 weeks. The smaller caliber grafts and those that had outflow obstruction showed significant degrees of intimal hyperplasia.

Experimental murine chromomycosis mimicking chronic progressive human disease.

Congenitally athymic (nu/nu) mice, mice defective in NK cell and macrophage function (bg/bg), and normal BALB/c mice were inoculated sc with 10 conidia of Fonsecaea pedrosoi (FP). In immunologically intact and immunodeficient mice, a local infection developed approximately 2 weeks post-inoculation and enlarged over 1-2 weeks. In bg/bg and normal nu/+ mice, lesions resolved within 5-6 weeks. However, nu/nu mice continued to have enlarging sc lesions during greater than 4-6 months of observation. These eventually metastasized. Lesions contained few hyphal elements and massive numbers of sclerotic bodies. Five weeks after inoculation, 10 conidia forming units/gm of tissue were recovered from lesions. Delayed type hypersensitivity and serum antibody to FP antigens were demonstrated. Adoptive transfer of lymphocytes from nu/+ mice was followed in 2 months by the resolution of the lesions.

Nocardial osteomyelitis: a case report and review of the literature.

The occurrence of human nocardiosis is increasing in both immunocompetent as well as immunosuppressed patients. A 63-yr-old male construction worker presented with complaints of left hip pain and rapidly enlarging masses on his left neck and chest. He had been treated for a pneumonia of unknown etiology 3 mo prior to admission. A debridement of the left femur was performed and the curetted material was positive for Nocardia asteroides. Osteomyelitis due to the hematogenous spread of Nocardia asteroides is rare, but will undoubtedly be seen with increasing frequency. The literature, as well as 11 reported cases of the hematogenous spread of this organism, are reviewed.

Primary lymphocutaneous Nocardia brasiliensis infection: three case reports and a review of the literature.

The occurrence of human nocardiosis is increasing in both immunocompetent as well as immunosuppressed patients. We report three rare cases of primary lymphocutaneous Nocardia brasiliensis infection. The mode of inoculation in each case was that of a puncture wound that occurred 1-3 wk prior to the development of the clinically apparent infections. The original clinical diagnosis was erroneous in each case. A review of 16 previously reported cases is presented as well as a discussion of appropriate medical therapy.

Primary left atrial myxosarcoma.

A patient in whom rapidly progressive congestive heart failure developed due to the presence of a left atrial myxosarcoma is described. The histologic picture is consistent with the hypothesis that cardiac myxoid tumors are neoplasms derived from undifferentiated cells found in the endocardium. Unfortunately, most cardiac malignancies are detected too late for curative resection, and palliation remains the mainstay of therapy.

Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response.

PURPOSE: To evaluate the hemodynamics and tissue response associated with stent placement in low-flow-velocity arteries. METHODS: Six self-expanding nitinol stents (5.5 mm caliber) were implanted transfemorally within the proximal segments of vertebral arteries (2.5 mm diameter) in six adult dogs during anticoagulative protection. RESULTS: Control angiograms demonstrated patency and 20% dilatation of all stented arteries. One artery was partially thrombosed 1 week later and subsequently showed a 50% stenosis. Throughout the observation period (4 to 9 months after stenting), the other five arteries remained patent without significant narrowing (< or = 15%). Small cervical muscle branches originating from the vertebral arteries within the stented segments remained patent. No major branch occlusions of the vertebrobasilar system were detected. Stent migration or kinking did not occur. MR studies of the brain 4 months after implantation revealed no infarcted areas. These findings were confirmed with brain sections. Stented artery specimens showed delayed stent dilatation. A comparison of the total mean thickness of intima covering the five 30- to 40-mm stents removed at 4, 6, and 9 months showed no significant difference (338, 332, and 389 microns, respectively). Histologic findings verified the macroscopic impression of a thicker intima at the inner curve of the stented artery segments and at the junctions of the stent filaments. The shortest (10 mm) stent had the thinnest neointimal growth (155 microns). Stented vessels showed compression of the media with atrophy, but without necrosis or perforation. Scanning electron photomicrographs revealed intact endothelial cell linings with typical elongated cells. CONCLUSIONS: No significant risk of thromboembolic events exists after implanting these nitinol stents in nonatherosclerotic vertebral arteries in dogs. Thicker neointimal growth after stenting may result from either low wall shear stress with possible flow separation or from changes in the shape and size of the stent, or both.

Filamentous Histoplasma capsulatum involving a ventriculoatrial shunt.

We describe the first case, to our knowledge, of filamentous Histoplasma capsulatum infection in a ventriculoatrial shunt. A review of the literature on the incidence, etiologies, and symptomatology of shunt-related infections is presented. The pathogenesis and treatment of the fungus-infected shunts are also discussed.

Luminal surfaces of fetal rat alveolar type II and Clara lung cells react with antibody to Heymann nephritis antigen.

We have used affinity purified antibody, which reacts with the renal antigen gp600, to examine the immunoreactivity of pulmonary cells in the quick frozen lung tissue of fetal rats. On immunoelectron microscopy, we found that the reaction was specifically localized to the luminal surfaces of Clara cell and, as previously reported, to alveolar type II cell (ATII) membranes. No immunoreaction was seen on or in type I cells, endothelial cells or any other lung or blood cell. These studies suggest that the anti-gp600 immunoselection can be used as a marker to identify and quantify Clara and ATII cells in rat lung tissue.

A randomized animal study evaluating the efficacies of locally delivered heparin and urokinase for reducing in-stent restenosis.

BACKGROUND: In-stent restenosis is primarily due to neointimal hyperplasia. Results from recent nonrandomized studies suggest that local delivery of heparin or urokinase to the site of angioplasty or stenting results in a lower rate of restenosis. OBJECTIVE: To determine whether local delivery of heparin or urokinase reduces in-stent restenosis. METHODS AND RESULTS: Thirty-three pigs were assigned randomly to one of three groups: controls (n = 9) administered local saline infusion, the heparin group (n = 15) administered local heparin (6000 u/10 min), and the urokinase group (n = 9) administered local urokinase (250000 u/10 min), via a local delivery catheter (Dispatch) at the site of subsequent stent implantation. Prior to local delivery, all of the animals were subjected to balloon injury (balloon:artery diameter ratio approximately or = 1.3) to facilitate intramural drug impregnation. After local therapy, one Palmaz-Schatz stent (mean stent: artery diameter ratio approximately or = 1.25) was implanted within the left anterior descending coronary artery. The degree of neointimal hyperplasia was evaluated 4 weeks later by angiography (as the maximal percentage diameter stenosis) and histology (as the maximal neointimal area stenosis). We found no difference in percentage diameter stenosis (46 +/- 18% control, 42 +/- 27% heparin group, and 37 +/- 20% urokinase group, P = 0.7) and corrected neointimal area (1.06 +/- 0.42 mm2 control, 0.94 +/- 0.29 mm2 heparin, and 0.88 +/- 0.26 mm2 urokinase group, P = 0.7) among groups at follow-up. The activated clotting time rose slightly for heparin-treated animals, suggesting that systemic delivery had occurred, whereas fibrinogen levels did not change in urokinase-treated animals. CONCLUSIONS: Local deliveries of heparin and urokinase via the Dispatch catheter, at the chosen dosages, do not reduce in-stent neointimal hyperplasia in this porcine model.

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.

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.