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C Herdeg

Publications and source records attributed to C Herdeg.

At least 19 recordsLinked to original sources
PubMed2002

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.

Aged↗
PubMed2002

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Angioplasty, Balloon↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Journal Article↗
PubMed2001

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.

Coronary Angiography↗
PubMed2001

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.

Adult↗
PubMed2000

[Results of a survey of 549 patients regarding long-term clinical outcome and quality of life four years after PTCA].

BACKGROUND: Quality control becomes increasingly important in interventional cardiology. Since in most health care systems, clinical treatment of patients who underwent percutaneous transluminal coronary angioplasty (PTCA) is left to general practitioners, important information on the clinical long-term outcome is lost for the cardiologic centers. Aim of this study was to evaluate the clinical status of these patients 4 years after treatment with a PTCA at our institution. PATIENTS AND METHODS: Inclusion criterion was the treatment with a PTCA within July 1, 1989 to June 30, 1991 (549 patients). A questionnaire was sent to all patients (45 +/- 7 months after PTCA). Four time-points were defined: before PTCA (T1), directly after PTCA (T2), 3 months after PTCA (T3) and actual status (T4). RESULTS: Questionnaires of 500/549 (91.1%) patients could be analyzed. One-hundred and fifteen patients (23%) had to undergo reinterventions: 69 (13.8%) had a re-PTCA and 46 (9.2%) patients an operative revascularization. At T4, 11.2% patients still had disturbing angina. Within the study period 35 patients (7%) died. Two-hundred and nineteen patients attended a rehabilitation institution. At T4, the amount of patients with little angina was not different comparing patients with/without the attendance of a rehabilitation institution (60.7% vs 66.4% p = 0.29). The rate of new pensioners after PTCA (n = 114 [22.8%]) was higher in the group of patients who attended a rehabilitation (68 patients [13.6%] with vs 48 patients [9.2%] without attendance, p = 0.0036). The attendance of a rehabilitation institution, however, had positive effects on changes of the life style and eating habits. CONCLUSIONS: This retrospective inquiry was found to be a useful tool (response rate 91.1%) for quality control in interventional cardiology. Important information concerning the quality of the interventions (low reintervention rate) and the long-term outcome of our patients (low rate with severe angina at T4) could be acquired.

Aged↗
PubMed2000

[Paclitaxel: a chemotherapeutic agent for prevention of restenosis? Experimental studies in vitro and 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.

Angiogenesis Inhibitors↗
PubMed2000

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.

Animals↗
PubMed2000

Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo.

OBJECTIVE: The aim of this study was to evaluate the potential of paclitaxel to prevent restenosis in vivo. BACKGROUND: Paclitaxel (Taxol) is a microtubule-stabilizing compound with potent antitumor activity. It influences the cytoskeleton equilibrium by increasing the assembly of altered microtubules, thereby inducing cellular modifications that result in reduced proliferation, migration and signal transduction. METHODS: Before the in vivo study, delivery efficiency was determined with radiolabeled paclitaxel in porcine hearts. After induction of a defined plaque in the right carotid arteries of 76 New Zealand rabbits by electrical stimulation, 27 animals underwent balloon dilation and subsequent local paclitaxel delivery (10 ml, 10 micromol/liter) with a double-balloon catheter. Twenty-nine animals served as control with angioplasty only, 10 animals underwent local delivery of vehicle only (0.9% NaCl solution) and 10 animals were solely electrostimulated. Vessels were excised one, four, and eight weeks after intervention. RESULTS: The extent of stenosis in paclitaxel-treated animals was significantly reduced compared with balloon-dilated control animals (p = 0.0012, one, four and eight weeks after intervention: 14.6%, 24.6% and 20.5%, vs. 24.9%, 33.8% and 43.1%, respectively). Marked vessel enlargement compared with balloon-dilated control animals could be observed (p = 0.0001, total vessel area after one, four and eight weeks: paclitaxel group: 1.983, 1.700 and 1.602 mm2, control: 1.071, 1.338 and 1.206 mm2, respectively). Tubulin staining and electron microscopy revealed changes in microtubule assembly, which were limited to the intimal area. Vasocontractile function after paclitaxel treatment showed major impairment. CONCLUSIONS: Local delivery of paclitaxel resulted in reduced neointimal stenosis and enlargement in vessel size. Both these effects contribute to a preservation of vessel shape and are likely to be caused by a structural alteration of the cytoskeleton.

Animals↗
PubMed2000

The impact of untreated coronary dissections on acute and long-term outcome after intravascular ultrasound guided PTCA.

AIM: Vessel size adapted PTCA results in the use of larger balloons with an increased incidence of severe vascular dissections. The aim of our trial was (a) to evaluate the effect of severe dissections on the acute outcome and (b) to study the natural history of dissections after 1 year. METHODS AND RESULTS: One hundred and seventy-eight patients with 195 lesions underwent vessel size adapted PTCA using intravascular ultrasound. Clinical and angiographic 1 year follow-up was obtained for all patients. Intravascular ultrasound was performed before PTCA to measure the external elastic membrane diameter at the lesion site so that the balloon size could be adopted (external elastic membrane-10%) and post-interventionally to determine the procedural success and the incidence of intracoronary dissections. Stent implantation was reduced to persistently flow limiting dissections (TIMI I, II). Dissections were detected by intravascular ultrasound in 128/195 (66%) lesions (by angiography in 111/195 [58%] lesions) and classified by intravascular ultrasound criteria into four groups: group I: no dissection (67 lesions [34%]), group II: mild dissections (21 lesions [11%]), group III: medium dissections (19 lesions [10%]) and group IV: severe dissections (88 lesions [45%]). Because of threatened vessel closure, GPIIb/IIIa antagonists were used in eight (4.5%) patients and a stent was implanted in two (1. 1%) patients. The cumulative event rate after 1 year was 12% and the global angiographic restenosis rate was 19%. The post-interventional evidence of severe dissections was associated with a decrease in clinical events during long-term follow up (group I: 13 events [19%] vs group IV: seven events [7%];P=0.03). This was also true for the occurrence of restenosis which was significantly lower in patients with severe dissections (group I: 19 [28%] lesions vs group IV:10 [11%] lesions;P=0.01). CONCLUSIONS: According to the theory of 'therapeutic dissections', our data suggest that substantial dissections following PTCA, which do not diminish antegrade blood flow, do not lead to an increase in acute or long-term events. The natural history of vessel injury seems to provide favourable wound healing without increase of restenosis. Thus, stenting for treatment of large dissections without flow limitation does not seem to be mandatory.

Acute Disease↗
PubMed1999

[The ultrasonic measurement of the endothelial function of the brachial artery in suspected coronary heart disease].

BACKGROUND AND OBJECTIVE: A positive correlation between the presence of coronary artery disease (CAD) and peripheral endothelial dysfunction (ED) of the brachial artery has been shown in several studies. Aim of the present study was to evaluate whether the non-invasive determination of ED could also be used as a screening test in patients suspected of having CAD. PATIENTS AND METHODS: 122 patients were included. 112 had an exercise-ECG before hospital admission. Preceding coronary angiography, FMD% was measured by high-resolution ultrasound (13 Mhz). Longitudinal scans of the brachial artery were done at rest, during reactive hyperemia and after the sublingual administration of nitroglycerin. RESULTS: In 101 of the 122 patients the presence of CAD was diagnosed by angiography, whereas 21 patients had normal coronary arteries. The extent of the vasodilation (FMD%) was found to be largely independent of the resting vessel diameters (FMD%/vessel diameter at rest: r = -0.32767 p = 0.0002). FMD% was significantly higher in patient without CAD than in the CAD group (7.01 +/- 3.5% vs. 3.73 +/- 4.11%, p < 0.001). Comparison of sensitivity and specificity to predict the presence of CAD between FMD% [sensitivity 71.3%, specificity 81%] and exercise-ECG [sensitivity 82.4%, specificity 57.1%] gave similar results. No correlation was found between the degree of the impairment of FMD% and the severely of CAD. CONCLUSION: The determination of peripheral ED was found to be a sensitive and specific measure for predicting the presence of CAD in our cohort. Since this approach is non-invasive, non-radioactive and cost-effective it warrants further evaluation of its role as an additional screening test in patients clinically suspected of having CAD.

Aged↗
PubMed1999

Reduction of restenosis by vessel size adapted percutaneous transluminal coronary angioplasty using intravascular ultrasound.

Restenosis following percutaneous transluminal coronary angioplasty (PTCA) remains a serious problem in interventional cardiology. Recent trials using stent implantation have proposed a reduction in restenosis, presumably due to a higher initial luminal gain. This study was conducted to evaluate if the short- and long-term results following conventional PTCA may be favorable, if balloon dilation was performed according to measurements gained by intravascular ultrasound (IVUS) (vessel size adapted PTCA). The use of intracoronary stents might be omitted if comparable long-term results could be achieved by this modified technique of balloon angioplasty. This unicenter and nonrandomized pilot trial was initiated in January 1995 with 252 patients who had 271 lesions. IVUS was performed before and after intervention to determine the external elastic membrane (EEM) diameter at the lesion site. The balloon catheter was sized according to the EEM diameter measured by IVUS (EEM 10%). The mean balloon diameter was 4.1 +/- 0.5 mm, the dilation time 130 +/- 60 seconds with a balloon pressure of 7.0 +/- 2.0 atm. Clinical acute and 1-year long-term follow-up were obtained for all patients and follow-up angiography in 71% of patients. Acute events occurred postinterventionally in 5 patients (2%). The cumulative event rate during long-term follow-up was 14%. The angiographic restenosis rate (diameter stenosis >50%) after 1 year was 19%. Vessel size adapted PTCA using IVUS led to favorable acute and long-term results with a low restenosis rate and a low 1-year clinical event rate. Despite dissections that occur frequently using large balloon sizes, an increased rate of major complications did not occur, indicating a safe procedure and substantiating the philosophy of "therapeutic dissections." The results need to be verified in a randomized trial.

Angioplasty, Balloon, Coronary↗
PubMed1999

Local drug delivery: impact of pressure, substance characteristics, and stenting on drug transfer into the arterial wall.

Injection parameters for local drug delivery are frequently determined by studies with marker substances. However, the pharmacologic properties of the actual drug may influence delivery efficiency and lead to different results. Aim of this study was to assess the delivery capacities of two device-drug combinations in order to verify this approach for further in vivo studies. Tritiated (3H) preparations (5 ml) of the hydrophylic low-molecular-weight heparin reviparin and the lipophilic taxane paclitaxel were injected into the left anterior descending artery of freshly explanted porcine hearts with the Infusasleeve II catheter system. A balloon support pressure of 6 atm and infusion pressures of 40, 60, 80, or 100 psi were used. In three additional groups, reviparin was injected following stent implantation and paclitaxel was injected prior to or following stent implantation. Arteries along with surrounding myocardium were harvested. The artery was carefully dissected, and artery and myocardium were separately homogenized, and activity was measured. Of the totally delivered activity, 0.09%+/-0.03% (40 psi) to 0.17%+/-0.13% (100 psi) of reviparin and 2.03%+/-0.67% (60 psi) to 2.68%+/-1.57% (100 psi) of paclitaxel were found in the vessel wall. The results for different injection pressures were not significantly different for either drug. The percentage activity delivered to the vessel wall was substantially larger in the paclitaxel group as compared to reviparin delivery (P < 0.01 at 60, 80, and 100 psi). The mean concentration of reviparin in the artery was 20 to 33 times higher than in the myocardium. For paclitaxel the factors were 110 to 243. Stent implantation prior to or following local delivery did not result in a different delivery efficiency. The results demonstrate that the characteristics of the delivered drug contribute largely to the delivery efficiency. Using identical injection parameters, drug concentrations in the arterial wall were significantly higher for the lipophilic paclitaxel as compared to the hydrophilic reviparin. Stenting of the artery did not influence delivery efficiency.

Animals↗
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↗