Analysis of muscle microcirculation in advanced diabetes mellitus by contrast enhanced ultrasound.

AIMS: Contrast enhanced ultrasound (CEUS) was recently established to quantify perfusion deficits in peripheral arterial disease (PAD). However, this approach was not suitable to assess microangiopathy of skeletal muscle, a major contributor to PAD in diabetic patients. We hypothesized that an optimized methodology would detect impaired microcirculation. METHODS: Ten patients with advanced diabetes mellitus (mean diabetes duration 21 years), 10 PAD patients, and 10 control subjects were enrolled consecutively. The arrival times of the contrast agent Sonovue after intravenous injection were assessed selectively in a small artery, muscle tissue and a muscle vein of the calf muscle. Contrast transit times (CTTs) were calculated as the differences between arrival times. RESULTS: The median CTT for artery-vein was significantly higher in the diabetes group (43 s) than in the PAD (22 s, p=0.007) and control groups (11 s, p<0.001, no value overlap). CTTs for artery-muscle and muscle-vein were shorter with highest median values in the diabetes group. CONCLUSIONS: We validated improved CEUS as consistent method to detect changes in the microvascular bed. This method may become a valuable tool to quantify impaired microcirculation in diabetes and help to improve patient care.

Occlusion of iatrogenic pseudoaneurysms with percutaneous ultrasound guided thrombin injection.

BACKGROUND: Pseudoaneurysm is a common complication of cardiac catheterization and coronary intervention with an incidence of 2% even in experienced centers. PATIENTS AND METHODS: In a feasibility study conducted between December 2004 and February 2006 we enrolled 76 patients consecutively to receive local thrombin injection (mean 329 IU; range 100-800 IU) into the aneurysma sac. RESULTS: Ultrasound guided thrombotic occlusion of pseudoaneurysms was successful after one injection in 83% of the patients, 17% of the patients required more than one injection. The overall success rate of the procedure was 98,9%. No peripheral embolisation of thrombin was noted during any injection and we registered no other complication that needed any further intervention. CONCLUSIONS: We conclude that ultrasound guided occlusion of pseudoaneurysms using thrombin injection with a success rate of the procedure of 98,9% is feasible and safe.

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.

Is the "candy-wrapper" effect of (32)P radioactive beta-emitting stents due to remodeling or neointimal hyperplasia? Insights from intravascular ultrasound.

A recognized limitation of radioactive stents is the development of restenosis at the stent edges, known as the "candy-wrapper" effect. The mechanisms of this effect remain incompletely understood and controversial. The aim of this study is to assess the effect of endovascular irradiation on neointima formation and vascular remodeling. (32)P Palmaz-Schatz stents (1.5-4 microCi) were implanted in 11 patients with restenosis after previous percutaneous transluminal coronary angioplasty (PTCA). Intravascular ultrasound (IVUS) images of target sites and adjunct vessel segments were acquired both during intervention and after 6 months. The angiographic restenosis rate was 54%, and the MLD decreased from 2.21 +/- 0.6 mm to 1.38 +/- 0.4 mm at follow-up (P < 0.01). IVUS analysis demonstrated that late lumen loss was the result of neointimal tissue proliferation, which was nonuniformly distributed and exaggerated at both the central articulation and the distal stent edges. Negative remodeling did not contribute to restenosis. In contrast, we found a linear relationship between increase of area stenosis and a positive remodeling index (r = 0.84, P < 0.0001). Restenosis after implantation of (32)P Palmaz-Schatz stents was mainly the result of neointimal tissue proliferation which tended to be nonuniformly distributed in the stent articulation and edges. Negative remodeling or stent recoil was not observed. Cathet Cardiovasc Intervent 2001;54:41-48.

Overestimation of stent delivery balloon diameters by manufacturers' compliance tables: a quantitative coronary analysis of Duet and NIR stent implantation.

Although manufacturers' compliance tables of stent delivery balloons indicate the diameter of the balloon at a given inflation pressure, it is unclear whether these data correlate with in vivo true intracoronary balloon diameters (TBDs). The TBDs of two new-generation balloon-expandable stent delivery systems (Duet and NIR) were measured by quantitative coronary analysis (QCA) in 100 consecutive patients. The manufacturers' stated balloon diameter (BD) of the stent delivery systems overestimated the TBD in 94% +/- 4% of patients receiving both Duet or NIR stent implantations. In only 6% of the patients, the TBD matched the manufacturers' stated balloon diameter. There was no underestimation of TBDs by both manufacturers' compliance tables. The Duet tables overestimated TBDs by 14% +/- 8% (range, 1%-36%), the NIR tables by 18% +/- 8% (range, 1%-41%), P < 0.05, Duet vs. NIR, respectively. When the manufacturers' data were corrected for the differences in reporting data from in vitro tests, i.e., balloon compliance data with or without the stent, the degree of overestimation of diameters was similar for Duet and NIR stent delivery balloons (14% +/- 8% vs. 13% +/- 7%, Duet vs. NIR; P = NS). Manufacturers' compliance tables of both the Duet and NIR stent delivery balloon systems significantly overestimate the true intracoronary balloon diameter. The manufacturers' of stent delivery balloons should clearly state on the box, if balloon compliance data were derived from in vitro bench testing, which phantoms were used for compliance analysis, and that the tables may overestimate the true intracoronary balloon diameter. The findings of the present study have important clinical implications with respect to performing coronary stent implantation with precision.

A novel balloon angioplasty catheter impregnated with beta-particle emitting radioisotopes for vascular brachytherapy to prevent restenosis; first in vivo results.

BACKGROUND: According to early clinical trials, vascular brachytherapy performed prior to or shortly after angioplasty is very effective in reducing restenosis rates. The purpose of this study was to investigate the effects of a novel radioactive catheter that allows simultaneous balloon angioplasty and beta-particle irradiation in the prevention of restenosis. MATERIAL AND METHODS: The balloon surface of an angioplasty catheter was impregnated with the radioisotope(32)P. Dosimetry calculations using a Monte Carlo method were performed at a radial distance of 0.2 mm from the balloon surface. Rabbit iliac arteries were dilated and simultaneously irradiated with a dose of 20 Gy delivered to the adventitia. Control arteries were only dilated and not irradiated. Neointimal areas, cell numbers and the perimeter of the arteries were measured by histomorphometry after 6 weeks. RESULTS: Neointima formation was reduced after balloon dilatation and simultaneous beta-particle irradiation using the(32)P impregnated angioplasty catheter as compared to balloon dilatation alone with a non-impregnated catheter (0.09+/-0.06 vs 0.27+/-0.09 mm(2)neointimal area and 168+/-45 vs 360+/-133 cells/0.05 mm(2)neointima, P<0.001 vs control, respectively). In addition, balloon dilatation with the(32)P impregnated angioplasty catheter increased the vessel perimeter as compared to balloon dilatation with a non-impregnated catheter (4. 7+/-0.2 vs 3.9+/-0.3 mm, P<0.001 vs control). CONCLUSIONS: Simultaneous balloon dilatation and vascular brachytherapy with a novel(32)P impregnated angioplasty catheter markedly reduces restenosis in vivo by preventing neointimal hyperplasia and constrictive vascular remodelling.

The impact of stent design and delivery upon the long-term efficacy of radioisotope stents.

Both gamma and beta irradiation delivered via a radioactive catheter-based line source have been shown to have efficacy in reducing restenosis. However, these catheter-based treatments have some limitations, including the safety of handling sources ranging from 30 mCi to 500 mCi. Alternatively, one could use a stent as the platform for local radiation delivery as a means to prevent restenosis. Experimental studies have demonstrated that stents ion implanted with the b-particle emitter 32P can reduce neointima formation. Clinical evaluation of the radioisotope stent began in the fall of 1996. Dose escalation studies have now been completed in approximately 250 patients with 32P, b-particle emitting stents ranging from 0.5 microCi to 24 microCi. Overall, these feasibility trials have demonstrated a clear, dose-dependent reduction of neointimal hyperplasia within the stent structure, but with an unanticipated finding of a relatively high incidence of restenosis at the stent margins. The purpose of this paper is to review the current status of radioactive stents, with an emphasis on the key elements of stent design and stent delivery that could impact the long-term efficacy of this device.

External beam radiation after stent implantation increases neointimal hyperplasia by augmenting smooth muscle cell proliferation and extracellular matrix accumulation.

OBJECTIVES: We sought to examine the effects of high volume external beam radiation (EBR) after stent implantation on neointimal hyperplasia, smooth muscle cell (SMC) proliferation, presence of inflammatory cells and expression of extracellular matrix (ECM). BACKGROUND: Endovascular irradiation has been shown to reduce restenosis rates after angioplasty in preliminary trials, but conflicting results have been reported for the effects of external beam irradiation. METHODS: Forty-three Palmaz-Schatz stents were implanted into iliac arteries of New Zealand White rabbits. The arteries were externally irradiated after stent implantation with a single dose of 8 Gy (at day 3) or 16 Gy in two fractions (8 Gy at days 3 and 4) by means of a linear accelerator. In the control rabbits, no radiation was applied after stent implantation. Smooth muscle cells, macrophages and ECM were studied by immunohistochemistry at one and 12 weeks after stent implantation. Collagen type I and biglycan messenger ribonucleic acid (mRNA) levels were assessed by Northern blot analysis at one week. Neointimal cell densities and arterial lumen stenosis were measured by histomorphometry at 12 weeks. RESULTS: At 1 week, SMC proliferation at the site of stent implantation was increased after EBR with 8 and 16 Gy (26 +/- 5%, 32 +/- 3% vs. 17 +/- 8%; p < 0.01, 16 Gy vs. control). External beam radiation with 8 and 16 Gy augmented SMC proliferation proximal and distal to the angioplasty site (11 +/- 3%, 14 +/- 3 vs. 6 +/- 1%; p < 0.01, 16 Gy vs. control). Collagen type I and biglycan mRNA levels were elevated in stented arteries after EBR with 16 Gy. At 12 weeks, a marked decrease in neointimal cell density (248 +/- 97 vs. 498 +/- 117 SMCs/0.1 mm2 neointima; p < 0.005 vs. control) was noted after EBR with 16 Gy. Irradiation with 8 and 16 Gy increased arterial lumen stenosis compared with nonirradiated control rabbits (45 +/- 7%, 55 +/- 9% vs. 33 +/- 7%; p < 0.05, 8 Gy and p < 0.001, 16 Gy vs. control). CONCLUSIONS: High volume external beam radiation at doses of 8 or 16 Gy causes restenosis by augmenting proliferative activity at and adjacent to the site of stent implantation, and by dose-dependent up-regulation of extracellular matrix expression. The study suggests that excessive matrix accumulation is an important determinant of failure of radiation therapy to prevent restenosis.

Dosimetry calculation for a novel phosphorus-32-impregnated balloon angioplasty catheter for intravascular brachytherapy.

PURPOSE: A phosphorus-32-impregnated balloon angioplasty catheter was used in a novel technique of simultaneous angioplasty and vessel irradiation. The 32P radionuclides were distributed on the surface of the balloon so that a certain amount of radiation was delivered while angioplasty was performed. Three-dimensional dosimetry and dose-time relationship needs to be established for the catheter so that quantitative dosimetric information is available for both clinical treatment and research investigation. METHODS AND MATERIALS: The 32P-impregnated balloon of an angioplasty catheter was assumed to have a cylindrical shape, and the radionuclides were assumed to be distributed uniformly on the curved surface of the cylinder. The dose rate at a point in space was computed by integrating the point dose-rate kernel of 32P over the radioactive surface of the balloon. The point dose-rate kernel was computed with Monte Carlo simulation of radiation transport. The energy spectra of 32P based on a mathematical model was used in the calculations. The three-dimensional dose distributions and dose-time relationships were calculated for balloons of various lengths and radii. RESULTS: At a short radial distance (e.g., 0.2 mm) away from the balloon surface, the dose distribution was uniform across a large portion of the balloon along the longitudinal axis, and dropped off rapidly at both ends of the balloon. Uniformity became worse as the radial distance increased. Uniformity was almost independent of balloon radius. The underdosed length at each end of the balloon was also almost independent of balloon length. In the central transverse plane, the dose reached a maximum at the surface of the balloon and then dropped off rapidly as the distance increases. Relative dose coverage outside the balloon was approximately independent of balloon radius and length, and the absolute dose coverage was approximately inversely proportional to balloon radius and length, assuming same total activity. CONCLUSIONS: Point dose-rate kernel of 32P beta emitter and the three-dimensional dose distributions of a 32P-impregnated balloon from an novel angioplasty catheter were calculated. A rule of thumb for dose calculation and dose coverage was established for simultaneous angioplasty and vascular brachytherapy with a 32P-impregnated balloon catheter.

The radioisotope stent for the prevention of restenosis.

The use of intracoronary stenting has revolutionized catheter-based revascularization of obstructive coronary artery disease. These devices provide excellent scaffolding, predictable immediate success with the creation of a large, dissection-free luminal cross-section and improved long-term outcomes, when compared to "plain old balloon angioplasty". Despite these improvements restenosis still occurs at unacceptable rate, particularly in smaller vessels and in longer lesions. In this article we review the concept of using a stent implanted with low activities of radioisotope as a means to inhibit the proliferative process that is believed to initiate in-stent restenosis. The potential advantages, as well as the limitations of this means of intravascular brachytherapy are reviewed. This approach has been shown to be effective in certain animal models of restenosis. The initial clinical results with the Phase I safety trials will be summarized. Future directions for this technology, including the evaluation of new stent designs and new radioisotopes will be discussed. The early clinical results with more than 170 implants of low activity 32P Palmaz-Schatz and BX radioactive stents have demonstrated excellent procedural and 30-day event-free survival. Further dose finding safety trials are anticipated in 1998. Implementation of a large scale randomized clinical trial will commence if and when early safety and efficacy data suggest a therapeutic effect from this technology. Thus, future studies will focus on optimal stent design and will evaluate alternative isotopes and dosing strategies.

[Prevention and treatment of restenosis after percutaneous transluminal coronary angioplasty]. / Prävention und Behandlung der Restenose nach perkutaner transluminaler Koronarangioplastie.

Restenosis is a clinical problem after coronary angioplasty associated with major ischemic events or repeat interventions in 20-50% of the patients undergoing this procedure. Major efforts have been undertaken in the past decade to successfully prevent or treat restenosis but no pharmacologic approach to the problem has as yet been identified to be effective enough in clinical conditions. New strategies to cope with restenosis are targeted by local application of ionizing radiation which markedly reduces cell proliferation after angioplasty in animal experiments. Preliminary clinical trials indicate that endovascular radiation therapy is a safe and effective means to treat restenosis. Randomized, multicenter studies with long follow-up periods are needed to support these early results.

[Catheter-assisted techniques for decreasing the rate of restenosis after coronary angioplasty: an overview of radiotherapy]. / Kathetergestützte Verfahren zur Verringerung der Restenoserate nach Koronarangioplastie: Ein Uberblick zur Strahlentherapie.

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a clinical problem associated with major ischemic events or repeat interventions in 20-50% of the treated patients. Systemic drug therapy has not yet been shown to prevent restenosis in clinical conditions. However, local therapeutic strategies are evolving, such as the catheter-based delivery of drugs, of antiproliferative genes, or of ionizing radiation. Experimental studies show that radiation therapy reduces restenosis rates, and preliminary clinical trials investigating a small number of patients indicate that, in particular, catheter-based radiation may be safe and effective. Randomized multicenter studies with long follow-up periods are needed to support these early results.

On the production of radioactive stents.

In the last few years, radioactive stents has been proved to inhibit neointima formation. This paper describes the actual status of producing such radioactive stents. After a short discussion of the different radioisotopes suitable for radioactive stents, potential production methods are discussed. The ion beam implantation of P-32 applied at the Karlsruhe Research Centre shall be described in more detail.

Apoptosis after stent implantation compared with balloon angioplasty in rabbits. Role of macrophages.

Both cell proliferation and apoptosis (programmed cell death) are supposed to play a role in restenosis after angioplasty. We studied these processes in smooth muscle cells (SMCs) and macrophages 1, 4, and 12 weeks after balloon angioplasty or Palmaz-Schatz stent implantation in rabbit iliac arteries. Proliferating cells were visualized by immunostaining with antibodies directed against proliferating cell nuclear antigen. Apoptotic cells were detected using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) technique, propidium iodide staining, and transmission electron microscopy. At all time points, the neointimal cross-sectional area of the arteries was twofold to fourfold greater after stent implantation than after balloon angioplasty. The total number of neointimal cells was similar 1 and 12 weeks after both interventions. The neointimal cell density, however, decreased by 58% between the 1st and the 12th week after stent implantation compared with a 20% decrease after balloon angioplasty (P < .01). Stent implantation induced more cell proliferation but also more apoptosis in the media than balloon angioplasty after 1 and 4 weeks. In addition, stent implantation caused more macrophage accumulation and apoptosis in the neointima, but cell proliferation rates did not differ significantly in comparison with balloon angioplasty. The higher rate of apoptosis in the neointima 1 week after stent implantation compared with balloon angioplasty is due to an increased rate of SMC and macrophage death. Macrophage accumulation and apoptosis in the early phase after stent implantation appear to play a role in extracellular matrix secretion, which increases neointima formation after 4 and 12 weeks compared with balloon angioplasty in this model.

Advantages and limitations of radioactive stents.

The concept of radioactive stents was initiated to prevent restenosis after angioplasty in patients with coronary artery disease. We review the modes of fabrication, dosimetry and the biological effects of radioactive stents. Radioactive stents deliver ionizing radiation continuously at very low-dose rates according to the half-life of the incorporated radioisotopes. The activity levels of radioactive stents are up to 10,000 times lower than activity levels of sources used for catheter-based vascular brachytherapy. Radioactive stents allow uniform dose distribution and precise dosimetry because of the direct source contact with the circumference of the vessel. Animal studies show that these stents can potently inhibit smooth muscle cell proliferation and neointimal hyperplasia. A persistent inhibition of neointimal hyperplasia appears to be dose dependent. Local or systemic side effects related to the irradiation were not observed. A limitation of radioactive stents could be the dose-dependent delay in stent endothelialization which, however, did not cause thrombotic vessel occlusion in animal experiments. Whether a delay in stent endothelialization is associated with an increased rate of occlusive stent thrombosis in humans requires further studies.

Pure beta-particle-emitting stents inhibit neointima formation in rabbits.

BACKGROUND: Considerable experimental evidence exists that neointimal hyperplasia after angioplasty is inhibited by gamma-irradiation of the treated arteries. A beta-particle radiation is absorbed in tissue within a shorter distance away from the source than gamma-radiation and may be more suitable for localized vessel irradiation. This study outlines a method to implant a beta-particle-emitting radioisotope (32P; half-life, 14.3 days) into metallic stents. The effects of these stents on the inhibition of neointimal hyperplasia was compared with conventional stents in a rabbit model. METHODS AND RESULTS: 32P was produced by irradiation of red amorphous phophorus (31P) with neutrons and was implanted into Palmaz-Schatz stents (7.5 mm in length) after being kept apart from 31P in a mass separator. The radioisotope was tightly fixed to the stents, and the ion implantation process did not alter the surface texture. Stent activity levels of 4 and 13 microCi were chosen for the study. Four and 12 weeks after placement of conventional stents and 32P-implanted stents in rabbit iliac arteries, vascular injury and neointima formation were studied by histomorphometry. Immunostaining for smooth muscle cell (SMC) alpha-actin was performed to determine SMC cellularity in the neointima. SMCs were quantified by computer-assisted counting of alpha-actin immunoreactive cells. Endothelialization of the stents was evaluated by immunostaining for endothelial cell von Willebrand factor. No difference in vessel wall injury was found after placement of conventional and 32P-implanted stents. Neointima formation was potently inhibited by 32P-implanted stents only at an activity level of 13 microCi after 4 and 12 weeks. Neointimal SMC cellularity was reduced in 32P-implanted stents compared with conventional stents. Radioactive stents were endothelialized after 4 weeks, but endothelialization was less dense than in conventional stents. CONCLUSIONS: Neointima formation in rabbits is markedly suppressed by a beta-particle-emitting stent incorporating the radioisotope 32P. In this model, a dose-response relation with this type of radioactive stent was observed, indicating that a threshold radiation dose must be delivered to inhibit neointima formation after stent placement over the long term.

Low-dose radioactive endovascular stents prevent smooth muscle cell proliferation and neointimal hyperplasia in rabbits.

BACKGROUND: Restenosis induced by smooth muscle cell (SMC) migration and proliferation and neointimal thickening limits the clinical success of balloon angioplasty and stent implantation. In this study, the long-term effect of endovascular irradiation via low-dose radioactive stents on neointima formation was compared with conventional stent implantation in a rabbit model. METHODS AND RESULTS: Palmaz-Schatz stents were made radioactive in a cyclotron. The stents had a very low activity (maximum, 35 microCi), and thus, manipulation did not require extensive radiation protection. One, 4, 12, and 52 weeks after the implantation of nonradioactive stents and radioactive stents in rabbit iliac arteries, neointimal thickening was analyzed by quantitative histomorphometry. Immunostaining for endothelial cell von Willebrand factor, macrophages, SMC alpha-actin, collagen type I, and proliferating cell nuclear antigen (PCNA) was performed to determine radiation-induced changes in the arterial wall. SMC proliferation was quantified by computer-assisted cell counting of PCNA-immunoreactive cells. Neointima formation was markedly suppressed by the implantation of radioactive stents in a dose-dependent fashion at all observed time points. At peak proliferative activity of SMCs 1 week after nonradioactive stent implantation, 30 +/- 2% of SMCs in the neointima were proliferating, compared with 0.5 +/- 0.1% of SMCs after implantation of stents with an initial activity of 35 microCi (P < .001). The neointima covering radioactive stents was characterized by decreased smooth muscle cellularity and increased extracellular matrix formation. Further, we observed a delayed endothelialization depending on the radiation dose. No difference in vascular thrombosis was found after nonradioactive and radioactive stent implantation. CONCLUSIONS: The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.

Influence of surface texture and charge on the biocompatibility of endovascular stents.

BACKGROUND: The mechanical behaviour and the surface characteristics of endovascular stents are key factors determining stent patency. In-vitro studies have suggested that surface texture and charge alter the biocompatibility of metallic stents. In this study, the influence of surface texture and charge of metallic stents on thrombosis and neointima formation was evaluated in a rabbit model. METHODS: Twenty-four stainless steel Palmaz-Schatz stents were coated either by an electrochemical deposition of metal on the stent surface or were coated with a metallic film which was implanted into the stent surface by argon ion bombardment. The coatings consisted of platinum, gold, or copper. Coated and uncoated control stents were implanted in rabbit iliac arteries. As antithrombotic therapy, 500 IU heparin and 60 mg aspirin was given intravenously before stent implantation, followed by 60 mg aspirin intravenously every third day for 4 weeks. Thrombus and neointima formation in arterial cross-sections of 24 coated stents were compared with 19 uncoated stents using quantitative, computer-assisted histomorphometry and transmission electron microscopy. RESULTS: A higher stent surface porosity and more surface cracks after stent expansion were found after galvanization than after ion implantation. The in-vitro surface potentials of uncoated steel, copper-, and gold-coated or platinized stents were +150, +120, +180, and +180 mV, respectively. Four weeks after implantation, six of 14 galvanized stents, but none of the uncoated or ion bombarded stents, were occluded by a thrombus. Neointimal hyperplasia was increased in stents coated by galvanization compared with stents coated by ion implantation. In both study groups, the most electropositive coating (platinum or gold) induced markedly less neointima formation than the least electropositive (copper). CONCLUSION: Stent surface texture was the most important factor determining biocompatibility of coated Palmaz-Schatz stents in this study. In contrast to suggestions derived from in-vitro studies, the charge of stents does not seem to play a major role with respect to stent thrombogenicity. Low stent charge correlates with an increased neointima formation.