Secondary prevention in diabetic and nondiabetic coronary heart disease patients: Insights from the German subset of the hospital arm of the EUROASPIRE IV and V surveys.

BACKGROUND: Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012-13; and EA-V, 2016-17) in Germany. METHODS: The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V). RESULTS: 384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%). CONCLUSION: Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.

The Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) score.

BACKGROUND: Recent studies suggest a high interindividual variability of response to clopidogrel associated with adverse cardiovascular outcome. Different clinical factors are considered to influence a persistent residual platelet aggregation (RPA) despite conventional antiplatelet therapy. OBJECTIVES: To investigate clinical factors that affect RPA after 600-mg clopidogrel loading in a large unselected cohort of patients with symptomatic CAD. METHODS: The study population included a consecutive cohort of 1,092 patients treated with coronary stenting for stable angina and acute coronary syndromes (ACS). Residual platelet activity was assessed by ADP (20 micromol L(-1))-induced platelet aggregation >or= 6 h after LD. Eleven clinical factors were included in the primary analysis. RESULTS: In multivariate regression analysis increased RPA was significantly influenced by ACS, reduced LV-function, diabetes mellitus, renal failure (creatinine > 1.5 mg dL(-1)), and age > 65 years. In a factor-weighed model the risk for high RPA increased with higher score levels (OR for patients with a score of 1-3, 1.21, 95% CI 0.7-2.1; score 4-6, OR 2.0, 95% CI 1.17-3.5; P = 0.01; score 7-9, OR 3.3, 95% CI 1.8-6.0). During a 30-day follow-up the incidence of major adverse events was higher in patients with RPA in the upper tertile (4.8% vs. 2.5% in the 2nd and 1.5% in the 1st tertile; P < 0.05). CONCLUSIONS: The PREDICT score provides a good tool to estimate residual platelet activity after clopidogrel LD by easily available patient details. Additionally, we demonstrate its association with short-term outcome. Thus, patients with a high score may benefit from intensified antiplatelet therapy by improved platelet inhibition and risk reduction for thromboischemic events.

Residual platelet activity is increased in clopidogrel- and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary artery disease.

OBJECTIVE: To evaluate residual platelet activity in a consecutive cohort of patients treated with dual antiplatelet therapy after coronary stent implantation DESIGN: Prospective single-centre cohort study. SETTING: University hospital in Germany. PATIENTS: 480 patients with symptomatic coronary artery disease (n = 221 (46%) or acute coronary syndrome (ACS; n = 259 (54%) stable angina) were studied. Platelet activity was measured by collagen- (5 microg/ml) and adenosine diphosphate- (ADP; 20 micromol/l) induced platelet aggregation to assess post-treatment activity in patients treated with acetylsalicylic acid (500 mg bolus intravenously followed by 100 mg once a day) and clopidogrel (600 mg loading dose followed by 75 mg once a day) MAIN OUTCOME MEASURES: Increased residual platelet activity (IRPA) was defined if platelet aggregation was in the upper tertile of values in the patient collective. Association of epidemiological factors with IRPA was evaluated in a multivariate logistic regression analysis. RESULTS: IRPA-ADP was found in 53 patients (11.0%) and IRPA-collagen in 42 patients (8.8%). ACS was associated with IRPA independently from other factors (for IRPA-collagen: odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2 to 4.5, p<0.05; for IRPA-ADP: OR = 2.4; 95% CI 1.3 to 4.4, p<0.01; for IRPA-ADP/collagen: OR = 4.5, 95% CI 1.2 to 16.9, p<0.05). CONCLUSIONS: The data suggest that ACS is independently associated with IRPA despite conventional antiplatelet therapy. Further studies are warranted to demonstrate the effects of intensified antiplatelet therapy for patients with acute coronary events.

Non-invasive evaluation of atherosclerosis with contrast enhanced 16 slice spiral computed tomography: results of ex vivo investigations.

OBJECTIVE: To evaluate the diagnostic accuracy of 16 slice computed tomography (CT) in determining plaque morphology and composition in an experimental setting. The results were compared with histopathological analysis as the reference standard. METHODS: Nine human popliteal arteries derived from amputations because of atherosclerotic disease were investigated with multislice spiral CT (MSCT). Atherosclerotic lesions were morphologically classified (completely or partially occlusive, concentric, eccentric), and tissue densities were determined within these plaques. In addition, vessel dimensions were quantitatively measured. RESULTS: The results were compared with histological analysis. The concordance index kappa for morphological classification was 0.88. Plaque density (n = 51 lesions) was significantly different (p < 0.0001) between lipid rich, fibrotic, and calcified lesions (Stary stage III: n = 2, 58 (8) Hounsfield units (HU); Stary V: n = 11, 50 (21) HU; Stary VI: n = 14, 96 (42) HU; Stary VII: n = 6, 858 (263) HU; Stary VIII: n = 18, 126 (99) HU). The concordance index kappa for the classification of plaques based on density was 0.51. Vessel dimensions had a good correlation (r = 0.98). CONCLUSIONS: 16 slice CT was found to be a reliable non-invasive imaging technique for assessing atherosclerotic plaque morphology and composition. Although calcified lesions can be differentiated from non-calcified lesions, the diagnostic accuracy in further subclassifying non-calcified plaques as lipid rich and fibrotic is low, even under experimental conditions.

Allergic cholestatic hepatitis and exanthema induced by metamizole: verification by lymphocyte transformation test.

We report about a 66-year-old-male patient who was hospitalized with generalized exanthema and increase of liver enzymes after intake of metamizole because of flue-like symptoms. Despite initial high dose steroids, disease activity persisted, and therefore liver biopsy was performed. Histology revealed acute hepatitis with perivenular non-bridging confluent necrosis and granuloma formation consistent with drug-induced hepatitis. A metamizole-induced process was suspected. Lymphocyte transformation test confirmed the sensitization of the patient's lymphocytes to metamizole and three of its four metabolites (4-methylaminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine). Other drugs could be excluded with high probability. In the follow-up, the general condition of the patient improved, and liver enzymes decreased under treatment with steroids. Thus, we conclude that in this patient metamizole has induced an allergic reaction not only of the skin but also of the liver. To our knowledge, an allergic cholestatic hepatitis caused by metamizole has been reported only once in literature.

Virtual coronary angioscopy using multislice computed tomography.

BACKGROUND: With faster image acquisition times and thinner slice widths, multislice detector computed tomography (MSCT) allows visualisation of human coronary arteries with diagnostic image quality. In addition to conventional axial slices, virtual coronary angioscopies (VCA) can be reconstructed using MSCT datasets. OBJECTIVE: To evaluate the feasibility of reconstructing VCA and to determine the clinical value of this new application in detecting atherosclerotic coronary artery lesions. METHODS: Datasets obtained by contrast enhanced non-invasive coronary angiography using MSCT (Somatom VZ) were analysed from 14 consecutive patients. VCA were simulated in 14 coronary arteries (left anterior descending, n = 7; right coronary, n = 7). Lesion detection was undertaken on conventional contrast enhanced axial slices, as well as by VCA. Intracoronary ultrasound (ICUS) was used as the gold standard for in vivo plaque detection. RESULTS: 38 lesions were detected both on ICUS and on axial slices: 14 severe target lesions of > 75% area stenosis (11 calcified, three non-calcified), and 24 intermediate lesions of < or = 75% area stenosis (seven calcified, 17 non-calcified). Using VCA, all severe lesions (n = 14) and all calcified intermediate plaques (n = 7) could clearly be identified. However, non-calcified intermediate lesions (n = 17) could not be accurately distinguished from the vessel wall; they were recognised as vessel wall alterations without significant luminal narrowing. CONCLUSIONS: Current MSCT technology allows reconstruction of VCA with good image quality. Despite a more anatomical view of heart and coronary vessels on three dimensional reconstruction, conventional axial slices were found to be superior for detecting coronary lesions. Thus further technical innovations are required before VCA can become a useful technique in clinical cardiology.

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.

Local delivery of paclitaxel using the double-balloon perfusion catheter before stenting in the porcine coronary artery.

Paclitaxel is a new cancer chemotherapeutic agent that has been approved for clinical use in patients with a variety of different cancers. Paclitaxel inhibits cell proliferation by an action on microtubules. The aim of this study was to evaluate the safety and efficacy of locally delivered paclitaxel after coronary stent implantation. A novel double-balloon perfusion catheter was used to deliver the drug locally in the pig coronary artery. Twenty-seven domestic pigs underwent stent implantation of the left anterior descending artery. In the treatment group (n = 11), paclitaxel (10 ml; 10 micromol/l) was delivered using the double-balloon perfusion catheter prior to stent implantation. The control group received stent implantation only (n = 16). The animals were sacrificed 4 weeks later. Vessels were perfusion-fixed and morphometric analysis was performed using conventional techniques. In addition, the extent of injury was determined at each stent-strut area. Correlation of local injury and neointimal thickness was evaluated by linear regression. Neointimal thickness (paclitaxel 1.0 +/- 0.4 vs. control 0.7 +/- 0.3 mm), neointimal area (paclitaxel 4.1 +/- 2.2 vs. control 2.4 +/- 1.1 mm(2)), and the lumen area (paclitaxel 2.1 +/- 1.9 vs. control 2.5 +/- 0.9 mm(2)) did not show significant differences between both groups. Medial area (3.3 +/- 2.3 vs. 1.6 +/- 0.4 mm(2)) was larger in the vessels treated with paclitaxel (P < 0.05). Linear regression failed to show any difference in the response to injury between the two groups. Local delivery of paclitaxel with the double-balloon-perfusion catheter did not reduce neointima formation following stent implantation in native pig coronary arteries.

Noninvasive detection of coronary lesions by multislice computed tomography: results of the New Age pilot trial.

The reliable noninvasive assessment of coronary artery disease would constitute an important step forward in clinical cardiology. The aim of the New Age pilot trial was to evaluate the diagnostic accuracy of multislice computed tomography (MSCT) in determining coronary lesions. As a gold standard for in vivo plaque detection, intracoronary ultrasound (ICUS) was used. Forty plaques were detected by ICUS in 15 target vessels (LAD, n = 8; RCA, n = 7) in patients assigned for ICUS-guided PTCA. Preinterventional MSCT was performed in all patients and the results were compared to ICUS with regard to lesion detection and quantification. According to ICUS results, the 40 plaques were divided into three groups: group I, mild lesions < 50% (n = 14; 44.36% +/- 5.77%); group II, intermediate lesions 50%-75% (n = 12; 59.18% +/- 9.39%); and group III, severe lesions > 75% (n = 14; 91.47% +/- 3.68%). All MSCT scans showed sufficient image quality for analysis. Thirty of 40 (75%) plaques were detected by MSCT in a first blinded session. After unblinding the ICUS results, the remaining 10 (25%) plaques could be identified. Lesion severity was classified correctly in 34 of 40 (85%) plaques. Plaque calcifications were diagnosed correctly in 16 of 19 (84.2%) plaques. Quantification of vessel size revealed a good correlation to the ICUS results (r(2) 0.68; P = 0.004). Noninvasive MSCT angiography showed good diagnostic accuracy with regard to lesion detection and quantification of vessel size. The overall good image quality, makes this new technology a promising modality, which might become an alternative diagnostic approach in patients with known or suspected coronary artery disease. Cathet Cardiovasc Intervent 2001;53:352-358.

Accuracy and reliability of quantitative measurements in coronary arteries by multi-slice computed tomography: experimental and initial clinical results.

AIM: To evaluate the accuracy of non-invasive measurements within coronary arteries by multi-slice computed tomography (MSCT). We present experimental as well as clinical data. MATERIALS AND METHODS: Silicon tubes simulating coronary arteries (outer diameter 6 mm, lumen diameter within stenotic area 2 mm) were used for experimental studies. Clinical data were derived from 15 patients in whom vessel diameters were assessed by MSCT, intracoronary ultrasound (ICUS) and quantitative coronary angiography (QCA). MSCT were performed in a Somatom Volume Zoom(trade mark)CT system (Siemens, Forchheim, Germany) at 2 collimated slice widths (2.5 mm, 1.0 mm). RESULTS: Outer silicon tube diameters were overestimated by MSCT (6.56 mm +/- 0.32 mm). All measurements revealed significantly better results on 1.0 collimation compared to 2.5 mm collimation (outer diameter: 6.36 mm +/- 0.22 mm vs 6.76 mm +/- 0.27 mm, P < 0.0001; lumen diameters: 1.83 mm +/- 0.14 mm vs 1.51 mm +/- 0.19 mm, P < 0.0001). The comparison of vessel diameters within human coronary arteries revealed comparable results between ICUS and MSCT (4.89 mm +/- 0.67 mm vs 4.91 mm +/- 0.71 mm, P = 0.79, r = 0.79, P < 0.0001). QCA-measurements showed significantly lower results (3.67 +/- 0.71, P < 0.0001, r = 0.62, P < 0.001). CONCLUSIONS: Experimental as well as initial clinical results indicate acceptable reliability and accuracy of quantitative measurements by MSCT, when using thin collimated slice widths. Partial volume effects lead to a systematic overestimation of vessel size. MSCT has the potential to become an important non-invasive diagnostic tool in patients with coronary artery disease.

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.

Primary cardiac leiomyosarcoma originating from the pulmonary valve. Case report and review of the literature.

Primary cardiac tumours are rare findings (incidence 0.02% according to a recent meta-analysis) with dismal prognosis. Approximately 25% are malignant, mostly represented by sarcomas. Among these, leiomyosarcomas are exceptional. Treatment for primary cardiac leiomyosarcomas consists of radical surgical resection followed by adjuvant radiation therapy and/or chemotherapy. The mean survival after surgery and adjuvant therapies is 6.8 months. We present a rare case of a 40- year-old male patient with a primary cardiac leiomysarcoma originating from the pulmonary valve. This patient died after surgery and implantation of a homograft of the pulmonary trunk. Furthermore, the literature has been reviewed.

Self-rated health and clinical status after PTCA: results of a 4-year follow-up in 500 patients.

Background: Data on the clinical long-term outcome of patients with coronary artery disease in the years following percutaneous interventions are rare. We therefore decided to conduct a study to: (1) analyze the efficiency of a retrospective inquiry using a questionnaire and (2) perform a clinical long-term follow-up of our patients. Methods and results: Some 45+/-7 months after PTCA, a questionnaire was sent to 549 patients who had been treated at our institution from July 1, 1989, to June 30, 1991. The response rate was 91.1%, with 49 patients (8.9%) lost to follow-up. A total of 115/500 patients (23%) had reinterventions due to severe angina (69 patients (13.8%) undergoing re-PTCA and 46 (9.2%) CABG). Sixteen patients (3.2%) had a myocardial infarction and 35 patients (7.0%) died. Multivariate analysis revealed that patients who were asymptomatic 3 months after PTCA were likely to have a good long-term outcome. This was not found when comparing the clinical status immediately after PTCA to follow-up. Medical therapy with beta-blockers/aspirin/lipid-lowering drugs decreased from 75.2/82.2/35.4% at hospital discharge to 54.6/76.7/25.2% at follow-up. Conclusions: The present study provided important quality data for our institution. The response rate to the questionnaire was surprisingly high (91.1%), indicating that retrospective inquiries may also be efficient. The rate of reinterventions during long-term follow-up (23%) was acceptably low. Good self-rated health 3 months after the intervention turned out to be a strong predictor for a good clinical long-term outcome. Furthermore, we observed an underuse of cardiac medication, something that will be the subject of further quality improvement measures.

Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography.

OBJECTIVES: The aim of the present study was to evaluate the accuracy in determining coronary lesion configuration by multislice computed tomography (MSCT). The results were compared with the findings of intracoronary ultrasound (ICUS). BACKGROUND: The risk of acute coronary syndromes caused by plaque disruption and thrombosis depends on plaque composition rather than stenosis severity. Thus, the reliable noninvasive assessment of plaque configuration would constitute an important step forward for risk stratification in patients with known or suspected coronary artery disease. Just recently, MSCT scanners became available for general purpose scanning. Due to improved spatial and temporal resolution, this new technology holds promise to allow for differentiation of coronary lesion configuration. METHODS: The ICUS and MSCT scans (Somatom Volume Zoom, Siemens, Forchheim, Germany) were performed in 15 patients. Plaque composition was analyzed according to ICUS (plaque echogenity: soft, intermediate, calcified) and MSCT criteria (plaque density expressed by Hounsfield units [HU]). RESULTS: Thirty-four plaques were analyzed. With ICUS, the plaques were classified as soft (n = 12), intermediate (n = 5) and calcified (n = 17). Using MSCT, soft plaques had a density of 14 +/- 26 HU (range -42 to +47 HU), intermediate plaques of 91 +/- 21 HU (61 to 112 HU) and calcified plaques of 419 +/- 194 HU (126 to 736 HU). Nonparametric Kruskal-Wallis test revealed a significant difference of plaque density among the three groups (p < 0.0001). CONCLUSIONS: Our results indicate that coronary lesion configuration might be correctly differentiated by MSCT. Since also rupture-prone soft plaques can be detected by MSCT, this noninvasive method might become an important diagnostic tool for risk stratification in the near future.

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.

Local delivery of a low molecular weight heparin following stent implantation in the pig coronary artery.

BACKGROUND: The low molecular weight heparin Reviparin reduces smooth muscle cell proliferation in cell culture experiments. Clinical studies with systemic application of the substance did not show a reduction of the incidence of restenosis following balloon angioplasty. Local delivery, by achieving higher local concentrations of the drug, may have the potential to decrease smooth muscle cell proliferation in the treated arterial segment. OBJECTIVES: The aim of this study was to investigate the effects of local delivery of reviparin following stent implantation in the pig coronary artery. METHODS: A coronary stent was implanted in the LAD of 34 pigs. In the treatment group 5 ml reviparin was injected with the Infusasleeve catheter at a proximal pressure of 80 psi. After 28 days the animals were sacrificed. Quantitative morphometric analysis comprised the intimal area, medial area and the lumen. The extent of vessel injury and the intimal thickness were assessed separately for each stent strut region. The correlation of injury and neointimal thickness was analysed using linear regression. RESULTS: There was no relevant difference in the extent of vessel injury (1.9 +/- 0.7 vs. 1.6 +/- 0.6), the neointimal areas (2.4 +/- 0.9 vs. 2.4 +/- 1.0 mm2) and the resulting stenosis (46 +/- 18 vs. 47 +/- 17%). The medial area was larger in the animals treated with local delivery (2.2 +/- 0.4 vs. 1.6 +/- 0.4 mm2; p < 0.01). The correlation of injury and neointimal thickness was comparable in both groups. In two animals the passage of the stent area with the delivery system resulted in stent dislocation and fatal subacute thrombosis. CONCLUSION: In this animal model, local delivery of reviparin with the Infusasleeve catheter did not result in a reduction of neointimal proliferation following stent implantation. Local delivery after stent implantation carries the risk of stent dislocation as a result of the passage with the delivery system.

[Paclitaxel: a chemotherapeutic agent for prevention of restenosis? Experimental studies in vitro and in vivo]. / Paclitaxel: Ein Chemotherapeutikum zur Restenoseprophylaxe? Experimentelle Untersuchungen in vitro und in vivo.

Paclitaxel, a potent anti-tumor agent, shifts the cytoskeleton equilibrium towards assembly of altered and extraordinarily stable microtubules. These cellular modifications lead to reduced proliferation, migration, and signal transduction. It is highly lipophilic, which promotes a rapid cellular uptake, and has a long-lasting effect in the cell due to the structural alteration of the cytoskeleton. This makes paclitaxel a promising candidate for local drug delivery intended to address the proliferative and migratory processes involved in restenosis. In this article, results of our in vitro and in vivo studies with paclitaxel are presented. Cell culture experiments with monocultures of human arterial smooth muscle cells as well as co-cultures with human endothelial cells showed that paclitaxel leads to an almost complete growth inhibition within a dose range of 1.0-10.0 mumol/l, even after a short (20 min) single dose application. The comparison of an active, semi-active, and passive delivery system (porous balloon, microporous balloon, and double balloon) favored the double balloon for the following in vivo experiments. Tubulin staining and electron microscopy enabled visualization of paclitaxel-induced vessel wall alterations. In the rabbit model, locally delivered paclitaxel resulted in reduced neointima formation and enlargement in vessel size; in the pig model, however, after stenting, this inhibition was not significant. Both reduced proliferation and enlargement in vessel size contribute to a preservation of vessel shape and are likely to be caused by a structural alteration of the cytoskeleton, which is also supported by vascular contraction force experiments.