Biomedical subjects

C Herdeg

Publications and source records attributed to C Herdeg.

32 records · Page 2Linked to original sources

PubMed1999

Visualization and comparison of drug effects after local paclitaxel delivery with different catheter types.

BACKGROUND: The microtubule stabilizing compound paclitaxel has proved to have potent antiproliferative effects on smooth muscle cells both in vitro and in vivo. It induces cellular modifications that result in reduced proliferation, migration and signal transduction by shifting the cellular microtubule equilibrium towards assembly. We therefore reasoned that a visualization of the altered cytoskeleton could enable an evaluation of the drug effects following local drug delivery. METHODS AND RESULTS: 3 catheters - the porous balloon, the microporous balloon and the double balloon catheter - were chosen for this study representing the spectrum from passive to active, pressure-driven delivery. After the induction of a defined plaque in the right carotid arteries of 40 New Zealand rabbits by electrical stimulation, 32 animals underwent balloon dilatation and 8 animals served as pre-interventional control group with electrostimulation only. In 24 animals (n = 8 in each group) subsequent local paclitaxel delivery (10 micromol/L) was performed. 8 animals served as control with angioplasty only. Vessels were excised 1 week following intervention. Immunohistochemistry with antibodies against bromodeoxyuridine, alpha-actin, macrophages, von Willebrand factor and alpha-tubulin was performed. Cytoskeletal changes were analyzed by electron microscopy. Tubulin staining and electron microscopy revealed changes with distinct staining patterns for the different catheters. Specific catheter-induced injuries could be identified for the porous and double balloon catheter. Intimal proliferation, percentage of macrophages and extent of injury favor the double balloon catheter for local paclitaxel delivery. CONCLUSIONS: The alterations of the cytoskeleton induced by paclitaxel allowed for the detection of drug action by staining of tubulin and electron microscopy. This enables an evaluation of transfer, distribution and drug effects directly in the vasculature without marker substances. The double balloon catheter appears to be best suited for local paclitaxel therapy.

Animals↗

PubMed1999

Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging.

BACKGROUND: Peripheral endothelial dysfunction (ED) quantified by the determination of flow-mediated dilation (FMD%) of the brachial artery with the use of high-resolution ultrasound is an early marker of atherosclerosis. Although a positive correlation with coronary artery disease (CAD) has been reported, the unanswered clinical question is the validity of FMD% as a screening test in patients with clinical suspicion of CAD. Thus the aim of this study was to determine the predictive value of FMD% compared with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. METHODS AND RESULTS: In this pilot study, we measured ED in 122 patients scheduled for coronary angiography by using high-resolution ultrasound (13 MHz). We defined ED as FMD% </=4.5%. The presence of CAD was defined as angiographically detectable atherosclerotic vessel alterations of any degree. Exercise electrocardiography and myocardial perfusion imaging had been performed on an outpatient basis. Statistical analysis was conducted by analysis of variance and Mantel-Haenszel chi-square test. Patients with CAD (n = 101) had a significantly lower FMD% than patients without CAD (n = 21; 3.7% +/- 4.1% vs 7.01% +/- 3.5%, P <.001). A sensitivity of 71%, a specificity of 81% with a positive predictive value of 0.95 (72 of 76), and a negative predictive value of 0.41 (17 of 46) was calculated. In comparison to angina pectoris (sensitivity 95%, specificity 47.6%), exercise electrocardiography (sensitivity 82.4%, specificity 57.1%) and myocardial perfusion imaging (sensitivity in our study group 100%) had the best specificity, and a high sensitivity for FMD% was found. CONCLUSIONS: The determination of ED was found to be a sensitive and specific screening test to predict the presence of CAD. Because this is a noninvasive, nonradioactive, and cost-effective approach, it warrants further evaluation to determine its value in daily clinical practice as an additional screening test in the diagnosis of CAD.

Angina Pectoris↗

PubMed1999

Frequency and efficacy of glycoprotein IIb/IIIa therapy for treatment of threatened or acute vessel closure in 1332 patients undergoing percutaneous transluminal coronary angioplasty.

BACKGROUND: Glycoprotein (GP) IIb/IIIa antagonists are potent inhibitors of thrombocyte aggregation and thrombus formation. Several large-scale randomized studies for prevention of thrombotic complications have shown their potential to reduce these complications in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). It was the purpose of this observational trial to assess the frequency and efficacy of primary GP IIb/IIIa antagonist therapy as a bailout procedure for the prevention of threatened or abrupt vessel closure in patients after conventional balloon angioplasty. METHODS AND RESULTS: From January 1995 to December 1996, PTCA was performed in 1332 consecutive patients with coronary artery disease. Overall, threatened or abrupt vessel closure was observed in 63 (4.7%) patients of the patient population. In these patients, abciximab was administered (0.25 mg/kg body weight intravenous bolus, followed by a 12-hour infusion at 10 mg/min). Repeat PTCA was performed shortly after the administration of the abciximab bolus to achieve an optimal flow at the time of active GP IIb/IIIa therapy. One day after intervention, early follow-up angiography was performed. Follow-up after 1 year included the clinical status of all patients and, if possible, control angiography. Overall, the preintervention minimum lumen diameter (MLD) measured 0.74 +/- 0.27 mm and the diameter stenosis was 75% +/- 24%. The postintervention MLD increased to 2.60 +/- 0.55 mm, and the diameter stenosis decreased to 24% +/- 22%. At 24-hour angiographic follow-up, the MLD decreased to 2.47 +/- 0.49 mm and the diameter stenosis increased to 28% +/- 24%, correspondingly. The thrombus score decreased from 2.8 +/- 1.5 before abciximab treatment to 0.88 +/- 0.81 after abciximab treatment, and Thrombolysis In Myocardial Infarction flow grade increased from 2.1 +/- 1.1 to 2.9 +/- 0.3. In-hospital events occurred in 2 patients. Both patients had to undergo emergency coronary artery bypass grafting (1 of these patients died). During long-term follow-up, there were 10 clinical events (1 death, 3 repeat PTCA, and 6 coronary artery bypass graft operations for restenosis at the target lesion site). The cumulative event rate after 1 year (including acute and follow-up events) for both the total group and for the target vessel was 19%. CONCLUSIONS: The results of this study demonstrate that GP IIb/IIIa antagonists are able to prevent vessel occlusion after PTCA complicated by subsequent threatened or abrupt vessel closure. In these situations, GP IIb/IIIa antagonists provide effective treatment for the reduction of thrombus at the target lesion site, which constitutes a second key element for threatened or abrupt vessel occlusion.

Abciximab↗

PubMed1998

Local and systemic delivery of low molecular weight heparin following PTCA: acute results and 6-month follow-up of the initial clinical experience with the porous balloon (PILOT-study). Preliminary Investigation of Local Therapy Using Porous PTCA Balloons.

The purpose of this study was to assess safety and feasibility of intracoronary delivery of reviparin using a porous balloon following percutaneous transluminal coronary angioplasty. The 2.7 mm porous balloon used in this study had 35 holes arranged in a spiral pattern. Eighteen patients (male n = 10, female n = 8, age 63 +/- 9 years) undergoing successful PTCA in coronary arteries with a vessel diameter of 2.5 to 3.0 mm determined by online QCA (LAD = 11, RCX = 3, RCA = 4) were included. They received a bolus of 7,000 anti-Xa-IU reviparin followed by local delivery of 1,500 anti-Xa-IU in 4 ml with an injection pressure of 2 atm. The patients received additionally 10500 anti-Xa-units intravenously during the following 24 hours and a daily dose of 7000 anti-Xa-units reviparin subcutaneously for the following 28 days. Angiograms were obtained before and after PTCA, directly after local delivery, at 24 hours postintervention and after 6 months. The primary success rate was 100%. Quantitative coronary angiography showed a minimum luminal diameter of 0.42 +/- 0.14 mm before PTCA, 1.87 +/- 0.45 after PTCA, 1.67 +/- 0.43 after LDD, 1.63 +/- 0.46 after 24 hours, and 1.06 +/- 0.6 after 6 months. Angiographic follow-up was obtained in all patients. No major complications occurred during the 6-month follow-up period. The angiographic restenosis rate was 28% (5/18) at follow-up. This study demonstrates safety and feasibility of local intracoronary delivery of reviparin with a porous balloon following PTCA even in smaller diameter coronary arteries.

Aged↗

PubMed1998

Local and systemic delivery of low molecular weight heparin stimulates the reendothelialization after balloon angioplasty.

OBJECTIVE: Recent investigations revealed the importance of endothelial cell integrity and function in the pathogenesis of restenosis after angioplasty. Agents which stimulate reendothelialization may prevent restenosis after interventional procedures. The results of in vitro studies suggested that heparin and low molecular weight heparin administration may enhance the recovery of the endothelium. In this study the extent of endothelial denudation and the occurrence and time course of endothelial regeneration after experimental balloon angioplasty followed by subcutaneous or local delivery of low molecular weight heparin was investigated. METHODS: A total of 102 rabbits were included in the study. An atheromatous plaque was induced by electrical stimulation in the right carotid artery of the animals. All animals underwent balloon angioplasty. Thirty-two rabbits received no further medical treatment. Twenty-five rabbits received subcutaneous low molecular weight heparin reviparin (400 anti-Xa-units/day) during the following 7 days. In 25 animals the dilated arterial segments were treated locally with reviparin (1500 anti-Xa-units/4 ml, 2 atm) using a porous balloon (2.5 mm, 35 holes, diameter 75 microns). Twenty animals served as control group without intervention. The vessels were excised 3, 7, 14, 28 and 56 days following intervention. Sections were stained with an antibody against von Willebrand factor and PECAM 1 to confirm the endothelial origin of the lining cells. After bromodeoxyuridine labeling, the extent of proliferation was determined by using a monoclonal antibody. In addition, morphometric analysis of the intimal and medial area was performed. RESULTS: Three days after balloon angioplasty histomorphological analysis showed a reduction of about 60% of the preinterventional endothelial cell number in all three groups. Already one week after intervention there was a significantly higher number of endothelial cells in both groups of low molecular weight heparin treated animals compared to the untreated group (s.c. group 144 +/- 33, local group 142 +/- 32 versus untreated 79 +/- 17 endothelial cells, p < or = 0.05). This significant difference was maintained during the following four weeks and demonstrated a 2-fold increase in endothelial proliferation in the heparin treated animals compared with the untreated group. In addition, immunohistological examination showed a significant decrease in smooth muscle cell proliferation in the s.c. and local reviparin treated animals and a subsequent reduction of intimal thickening. CONCLUSION: Local delivery of low molecular weight heparin promotes reendothelialization and contributes to the inhibition of smooth muscle cell proliferation.

Administration, Cutaneous↗

PubMed1997

Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery.

BACKGROUND: The antineoplastic compound paclitaxel (Taxol) causes an increased assembly of extraordinarily stable microtubules. The present study was designed to characterize the effects of paclitaxel on proliferation and migration of human arterial smooth muscle cells (haSMCs) in vitro and on neointima formation in an in vivo experimental rabbit model. METHODS AND RESULTS: Both monocultures of haSMCs and cocultures with human arterial endothelial cells (haECs) were used. Cell growth after 4, 8, and 14 days was determined in the absence or presence of platelet-derived growth factor-AB (PDGF-AB), basic fibroblast growth factor (bFGF), or thrombin. Nonstop paclitaxel exposure, as well as single-dose applications of paclitaxel for 24 hours or even 20 minutes (0.1 to 10.0 micromol/L), caused a complete and prolonged inhibition of haSMC growth up to day 14, with an IC50 of 2.0 nmol/L. Mitogens or cocultures with stimulating haECs did not significantly attenuate paclitaxel-induced effects. Immunohistochemistry showed characteristic cytoskeletal changes predominantly in the microtubule network. Additionally, in 20 male New Zealand White rabbits, intimal plaques were produced by electrical stimulation. In 10 animals, paclitaxel was locally applied by use of microporous balloons. Histologically, the intima wall area, wall thickness, and degree of stenosis were reduced significantly in paclitaxel-treated animals compared with controls. CONCLUSIONS: Our data show that paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner in monocultures and cocultures even in the presence of mitogens. Furthermore, paclitaxel prevents neointima formation in rabbits after balloon angioplasty. The long-lasting effect after just several minutes' exposure time makes this lipophilic substance a promising candidate for local antiproliferative therapy of restenosis.

Animals↗

PubMed1997

Time course of smooth muscle cell proliferation after local drug delivery of low-molecular-weight heparin using a porous balloon catheter.

It has been reported previously that systemic application of low molecular weight heparin (LMWH) suppresses smooth muscle cell (SMC) proliferation after balloon angioplasty in experimental studies. However, the high concentration of heparin required for a beneficial effect may cause severe bleeding complications. The ideal situation to overcome the systemic side effects would be to administer LMWH locally and deep into the arterial wall, which became possible by the development of porous balloon catheters. The in vivo feasibility of local delivery of LMWH using the porous balloon has been assessed by delivering tritium-marked LMWH into rabbit carotid arteries. The efficacy of the system was investigated by using a second injury animal model. After development of an intimal plaque by electrical stimulation, 61 rabbits were treated with the porous balloon after balloon angioplasty. In 23 rabbits, local drug delivery was accomplished with a porous balloon catheter (35 holes, hole diameter 75 microns, 2.5 mm catheter diameter). LMWH was locally administered with 4 ml (solution 375 anti-Xa-units/ml) and 2 atm. To study the extent of restenosis and morphological changes, these animals were killed 3, 7, 14, 28, or 56 d after intervention. After staining (hematoxylin, van Gieson, BrdU, RAM 11, alpha-actin) procedures to quantify SMC proliferation, intimal macrophages and morphological analysis were performed. Porous balloon treatment led to an increase in intimal SMC proliferation rate in the early stage after intervention. However, during the following time period, a significant decrease of the proliferation rate as compared with the animals treated with balloon angioplasty alone could be observed, which resulted in an only moderate increase of the intimal layer after local drug delivery compared with balloon angioplasty alone.

Angioplasty, Balloon↗

PubMed1997

Efficacy of low-molecular-weight heparin delivery with the Dispatch catheter following balloon angioplasty in the rabbit iliac artery.

Local drug delivery can be achieved with active injection systems or passive contact of a compound with the arterial wall. The Dispatch catheter allows for passive diffusion of drugs from drug compartments while preserving blood flow through the central conduit. The aim of this study was to investigate whether a reduction in neointima formation can be achieved by local delivery of a limited amount of a highly concentrated solution of the low-molecular-weight heparin Reviparin. In 16 New Zealand white rabbits, successful balloon dilatation was performed in both iliac arteries, followed by local delivery of 4 ml Reviparin (1,000 IU/ml). The arteries were harvested at 7, 28, or 56 d following the procedure. The intimal cell layers increased substantially between 7 and 28 d following balloon dilatation with or without local drug delivery. The medial cell layers showed only a little increase. Proliferation of smooth muscle cells reached an early peak after 7 d, with a significantly higher proliferation index following local delivery. The maximum amount of macrophages in the intima and media was detected after 28 d. The lumen area decreased with time and was 0.6 +/- 0.7 mm2 in the local delivery group at 56 d compared with 0.5 +/- 0.5 mm2 in the control group. In conclusion, local delivery of Reviparin with the Dispatch catheter is safe and feasible. However, the infusion of highly concentrated low-molecular-weight heparin over a short period of time did not result in a reduction of neointima formation and restenosis following balloon dilatation in the rabbit iliac artery.

Angioplasty, Balloon, Coronary↗

PubMed1997

Local drug delivery with porous balloons in the rabbit: assessment of vascular injury for an improvement of application parameters.

OBJECTIVES: Sufficient intramural drug concentrations with the use of porous balloon catheters can be achieved with additional vascular trauma only. However, effective delivery of a potent drug even in deeper layers of the vessel wall might outweigh these traumatic side effects. Given the porous balloon catheter, the parameters of injection pressure and applied fluid volume will influence the interventional result. METHODS: We tested a 2.5-mm porous balloon (35 75-micron pores) in the right carotid artery of New Zealand rabbits and used injection pressures of 1, 2, and 5 atm and fluid volumes of 2 and 4 ml of low-molecular-weight heparin solution in combination with the different parameters (n = 5 animals/group). In 50 rabbits, an intimal fibromuscular plaque was induced by using the electrostimulation model. Balloon dilatation and then application of the porous balloon was performed in 30 animals, 10 animals were only electrostimulated, and 10 animals served as a control group with balloon dilatation only. The vessels were excised 7 d after intervention, stained, and analyzed histomorpologically. Anti-Xa assays revealed the extent of systemically escaped drug, and serial cuts allowed for exact determination of vessel wall injuries. RESULTS: Effective local drug delivery could not be achieved with an injection pressure of less than 2 atm. Specific pressure-driven effects such as jet injuries could be identified. When the pressure was high enough for disruptive drug delivery (> or = 2 atm), fluid volumes of 4 ml led to loose elastic membranes and local thickening within the media. CONCLUSIONS: Sufficient intramural drug distribution using porous balloon catheters can be achieved with low injection pressures. Different fluid volumes strongly determine the extent of additional vascular injury.

Angioplasty, Balloon, Coronary↗

PubMed1996

Porous balloon delivery of low molecular weight heparin in the dog coronary artery.

UNLABELLED: The aim of this experimental study was to assess the safety of local delivery of low molecular weight heparin via a porous balloon in the canine coronary artery. In 16 mongrel dogs, percutaneous transluminal coronary angioplasty was performed. In addition, eight of the dogs were given 4 ml Clivarin (1500 IU) delivered locally into the coronary artery immediately after dilatation. The animals were killed after 3 or 14 days. In the animals with local administration, the results of histopathology after 3 days showed the findings to be heterogeneous with marked disruption of the internal elastic lamina in all animals, and varying degrees of medial haemorrhage, medial necrosis, perivascular haemorrhage and signs of myocardial necrosis. Similar changes, but of lesser severity, were present in the animals treated with balloon dilatation only. After 14 days, the severity of vascular and perivascular alterations (medial haemorrhage, perivascular haemorrhage, thrombus formation) was significantly lower in the local delivery group (P < 0.05), but disruption of the internal elastic lamina, as a marker of the initial trauma, was present in all the animals. The presence of residual intracoronary thrombus was only seen in the PTCA group without local delivery. CONCLUSIONS: In this safety study, both groups showed pronounced alterations in the vessel wall 3 days following percutaneous transluminal coronary angioplasty. This changed 14 days following percutaneous transluminal coronary angioplasty when intramural injection of Clivarin resulted in a marked decrease of residual thrombus and medial as well as perivascular haemorrhage. Although the additional vessel trauma by the drug delivery technique did not result in increased complications, a careful approach with this potentially harmful procedure is essential.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Inhibition of smooth muscle cell proliferation after local drug delivery of the antimitotic drug paclitaxel using a porous balloon catheter.

Percutaneous transluminal coronary angioplasty is an accepted treatment for coronary artery disease. The major limitation, however, is the high incidence of restenosis which limits the long-term benefit of this intervention. Paclitaxel is a new antiproliferative agent that has generated considerable scientific interest since it was introduced in clinical trials in the early 1980s. Recent in vitro studies have shown that paclitaxel has considerable antiproliferative activity in human coculture systems. In the present study the efficacy of paclitaxel was investigated after development of an intimal plaque by electrical stimulation and additional cholesterol diet and subsequent balloon angioplasty in 63 New Zealand White rabbits. Local drug delivery of paclitaxel was accomplished in 30 rabbits with a porous balloon catheter (35 holes, hole diameter 75 microm, 2.5 mm catheter diameter). Paclitaxel was administered locally with 4 ml (solution 10(-5) mol/L) using an injection pressure of 2 atm. To study the extent of restenosis and morphological changes, the animals were sacrificed 7, 28 or 56 days after intervention. After staining procedures quantification of SMC proliferation, intimal macrophages and morphological analyses were performed. Paclitaxel plasma concentrations were measured using HPLC technique. One week after balloon angioplasty the arteries treated with local paclitaxel delivery showed an insignificant trend towards a reduction in intimal smooth muscle cell proliferation (untreated 8.4 +/- 4.9 % vs paclitaxel treated 2.4 +/- 2.4 %, p = NS). However, this resulted in a significant reduction of stenosis degree of 66 % 8 weeks after intervention compared to the untreated group (untreated 41 +/- 18 % vs paclitaxel treated 14 +/- 11 %, p = 0.005). In conclusion, locally delivered paclitaxel prevented neointimal thickening in the rabbit carotid artery after balloon angioplasty. Local paclitaxel treatment may therefore be a clinical option for the prevention of restenosis after coronary interventions. However, further preclinical studies have to prove long-term efficacy and safety.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Influence of vessel size, age and body mass index on the flow-mediated dilatation (FMD%) of the brachial artery.

BACKGROUND: The non-invasive determination of the endothelial dysfunction (ED) of the brachial artery is a widely used method in clinical research. It remained, however, unclear, whether the test-results are influenced by the anatomical vessel size, the patients age, body mass index (BMI) or gender. METHODS: The flow-mediated vasodilatation (FMD%) of the brachial artery was determined in 122 consecutive (88 male, 34 female) patients. FMD% was measured using high resolution ultrasound (13 Mhz) at rest, during reactive hyperaemia and after the sublingual administration of glycerolnitrate (GTN%). RESULTS: Lumen diameters at rest varied from 2.48 mm to 6.33 mm (4.46+/-0.74 mm). The extent of FMD% as well as of GTN% showed an inverse correlation to the resting lumen diameters (r=-0.33, P<0.001/r=-0.51, P<0.001). This correlation was even more distinct in females (females: FMD% r=-0.54, P<0.001; GTN% r=-0.64, P<0.001 vs. males: FMD% -0.23, P<0.001; GTN% -0.59, P<0. 001). No significant influence of age (61+/-9 years, FMD%: r=-0.04, P=0.68, GTN%: r=-0.18, P=0.05) and BMI (27.03+/-3.43 kg/m(2), FMD%: r=0.16, P=0.08, GTN%: r=0.09, P=0.3) on the test results were found. CONCLUSIONS: FMD% was found to be rather independent of age or BMI. The anatomical vessel size had an influence on the test results, which was more obvious in female patients. Our data indicate the necessity of further methodological studies, in larger, community-based populations. In particular, it needs to be clarified, whether vessel size or even gender-specific correction factors are required when using this technique in routine clinical practice.

Adult↗

PubMedDate not supplied

Accuracy of density measurements within plaques located in artificial coronary arteries by X-ray multislice CT: results of a phantom study.

PURPOSE: Clinical studies indicate that coronary plaque morphology might be differentiated noninvasively using multislice CT by determining tissue density within the lesions. The aim of the present experimental study was to evaluate factors that influence density measurements within small vessels. METHOD: A coronary phantom model was developed, consisting of silicon tubes (lumen diameter 4 mm) with two plaques of known density inside, simulating soft and intermediate lesions (Plaque 1: -39 HU; Plaque 2: 72 HU). Density measurement were conducted in three different contrast medium concentrations (1:30, 1:40, 1:50) and two different slice widths (4 x 2.5 mm, 4 x 1 mm). All scans were performed on a Somatom Volume Zoom (Siemens, Forchheim, Germany). Experimental results were compared with calculated data based on computer simulation. RESULTS: The two plaques could be clearly differentiated from each other on both collimations (4 x 2.5 mm: Plaque 1, 85 +/- 61 HU vs. Plaque 2, 119 +/- 26 HU, p < 0.0001; 4 x 1 mm: Plaque 1, 50 +/- 54 HU vs. Plaque 2, 91 +/- 17 HU, p < 0.0001). Significantly lower and more accurate results were achieved with 1.0 mm collimation (p < 0.0001). Contrast medium concentration contributed significantly to the measurements (p < 0.001). The experimental findings were confirmed by computer simulation, which revealed even more accurate results when using a 0.5 mm collimation (Plaque 1, 0.5 mm: -9 HU vs. 4 x 1 mm: 14 HU, Plaque 2, 4 x 0.5 mm: 83 HU vs. 4 x 1 mm: 93 HU). CONCLUSION: Density measurements were found to be highly dependent on slice width and surrounding contrast enhancement. Our results indicate that standardization of methodology is required before the noninvasive differentiation of human plaque morphology by multislice CT can be applied in the clinical setting as a screening test for coronary soft plaques.

Analysis of Variance↗

PubMedDate not supplied

Antiproliferative stent coatings: Taxol and related compounds.

The implantation of stents can prevent vessels from post interventional elastic recoil and appears to limit adverse remodelling. In order to inhibit in-stent restenosis, an additional release of antiproliferative agents from the stent itself might lead to a synergistic reduction of lumen renarrowing. Paclitaxel (Taxol) is a microtubule-stabilizing agent with potent antiproliferative activity. Unlike other antimitotic agents of the colchicine type, it shifts the microtubule equilibrium towards assembly, leading to reduced proliferation, migration and signal transduction. Moreover, important biological processes, such as the activation of some protein kinases, are associated with microtubule depolymerization and are therefore inhibited by paclitaxel. Several experimental in vitro and in vivo studies using local paclitaxel delivery to inhibit proliferation and lumen renarrowing have been performed already--with very encouraging results.

Animals↗