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Biomedical subjects

K R Karsch

Publications and source records attributed to K R Karsch.

At least 37 records · Page 2Linked to original sources
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

[Use of Abciximab in threatening vascular occlusion after PTCA].

UNLABELLED: The administration of GP IIb/IIIa antagonists has been shown to be effective in reducing myocardial infarction and cardial death when given before PTCA. This prospective study was performed to determine the efficacy of abciximab in a bail-out situation to manage threatened or acute vessel closure. METHODS: Acute or threatened vessel closure was observed in 104 (5.5%) out of 1903 consecutive patients treated with PTCA in our institution. Of the 104 patients 46 (44%) were treated for unstable angina (CCS IV). Abciximab was administered in bail-out situations in a dosage of 0.25 mg/kg given as a bolus, which was followed by an intravenous infusion of 10 micrograms/min over 12 hours. Repeat PTCA was performed shortly after the administration of the abciximab bolus. After the procedure, the sheath was left in place and control angiography was carried out 24 h later. RESULTS: In 100 of the 104 patients TIMI flow III could be restored by abciximab therapy and RePTCA. In 4 patients an additional stent implantation was necessary due to persistent flow limitation. One day post PTCA, early follow-up angiography demonstrated patency of all vessels except two. In-hospital events occurred in 4 patients. Three of these patients underwent emergency CABG due to subacute vessel closure a few hours after PTCA and died during or directly after surgery. Follow-up after one year included clinical status and control angiography of the target vessel. During long-term follow-up, MACE occurred in 15 patients (2 MI, 8 CABG and 5 RePTCA). CONCLUSION: The results of this prospective trial demonstrate the efficacy of abciximab therapy in bail-out situations occurring during or early after PTCA. The use of abciximab in bail-out situations appears clinically beneficial. Further studies have to compare the efficacy of this approach with prophylactic abciximab treatment.

Abciximab↗
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↗
PubMed2000

Effects of cerivastatin on human arterial smooth muscle cell proliferation and migration in transfilter cocultures.

Statins competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity reducing mevalonate synthesis. In this study, antiproliferative and antimigratory effects of the new compound cerivastatin were analyzed and compared with classic statins of the first and second generation using mono- and cocultures of human arterial smooth muscle (haSMC) and endothelial (haEC) cells. Effects on the mitotic index and mitochondrial activity of haEC and haSMC monocultures were tested using BrdU enzyme-linked immunosorbent assay (ELISA) and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) tests, respectively. In lactate dehydrogenase (LDH) assays, cytotoxicity of statins was studied. Transfilter cocultures were performed for 14 days to evaluate haSMC growth under the stimulatory effect of proliferating haEC, which release growth factors [e.g., platelet-derived growth factor (PDGF)]. The hydrophobic statins simvastatin, lovastatin, and atorvastatin significantly inhibited haSMC and haEC growth in monocultures at 0.5-50 microM. However, most potent effects were exerted by cerivastatin in 10- to 30-fold lower doses without any significant cytotoxicity. More important, cerivastatin showed also significant effects on haSMC proliferation and migration in transfilter cocultures at extremely low doses (IC50, 0.04-0.06 microM), even when applied exclusively to the endothelial side and in the presence of low-density lipoprotein (LDL). Addition of mevalonate abolished the effects of cerivastatin completely. Even in the presence of growth-stimulating haEC and LDL, cerivastatin was found to be the most potent inhibitor of haSMC proliferation and migration in doses that also can be reached in human serum after oral drug administration. The results support the concept that statins seems to influence additional cellular mechanisms beyond cholesterol reduction, which might also have a relevance for the prevention of restenosis.

Analysis of Variance↗
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

Clinical significance of thrombocytopenia during a non-ST-elevation acute coronary syndrome. The platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial experience.

BACKGROUND: The significance of thrombocytopenia in patients experiencing an acute coronary syndrome (ACS) has not been examined systematically. We evaluated this condition in a large non-ST-elevation ACS clinical trial, with particular interest paid to its correlation with clinical outcomes. METHODS AND RESULTS: Patients presenting without persistent ST elevation during an ACS were randomized to receive a double-blind infusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor eptifibatide or placebo in addition to other standard therapies including heparin and aspirin. The primary end point was death/nonfatal myocardial infarction (MI) at 30 days, whereas bleeding and stroke were the main safety outcomes. Thrombocytopenia (nadir platelet count <100x10(9)/L or <50% of baseline) occurred in 7.0% of enrolled patients. The time to onset was a median of 4 days in both treatment arms. Patients with thrombocytopenia were older, weighed less, were more likely nonwhite, and had more cardiac risk factors. These patients experienced significantly more bleeding events: they were more than twice as likely to experience moderate/severe bleeding after adjustment for confounders. Univariably, ischemic events (stroke, MI, and death) occurred significantly (P<0.001) more frequently in patients with thrombocytopenia; multivariable regression modeling preserved this association with death/nonfatal MI at 30 days. Neither the use of heparin or eptifibatide was found to independently increase thrombocytopenic risk. CONCLUSIONS: Although causality between thrombocytopenia and adverse clinical events could not be established definitively, thrombocytopenia was highly correlated with both bleeding and ischemic events, and the presence of this condition identified a more-at-risk patient population.

Acute Disease↗
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

Occurrence of a saccular pseudoaneurysm formation two weeks after perforation of the left anterior descending coronary artery during balloon angioplasty in acute myocardial infarction.

We describe the occurrence of a localized saccular pseudoaneurysm in a 69-year-old patient 2 weeks after perforation of the left anterior descending coronary artery during balloon angioplasty in acute myocardial infarction. The therapy of perforations requires prolonged balloon inflations, perfusion balloons, covered stents, or surgery. Coronary peudoaneurysm formations are rare; their therapy requires covered stents or surgery. Cathet. Cardiovasc. Intervent. 47:341-346, 1999.

Aged↗
PubMed1999

[Risk of invasive diagnosis with retrograde catheterization of the left ventricle in patients with acquired aortic valve stenosis].

In patients with aortic valve stenosis, the determination of the transstenotic pressure gradient is usually performed by cardiac catheterization with retrograde passage of the aortic valve. The aim of this study was to determine retrospectively the risk of the invasive examination with retrograde catheterization of the left ventricle and predictors for an increased risk. From 1984 to 1995, 457 patients (63 +/- 11 years) with aortic stenosis were investigated in the Medizinische Klinik Tübingen. In 435 patients (95.2%), the retrograde catheterization of the left ventricle was successful; in 19 cases a transseptal left heart catheterization was performed, and in 3 patients an invasive determination of the pressure gradient was not assessed. Complications occurred in 39 patients (8.5%). 5 patients died due to the catherization procedure (mortality rate 1.1%), 2 of them as a consequence of perforation of the left ventricle, one patient of heart failure, one of myocardial infarction, and another of fulminant pulmonary embolism. Four procedures (0.9%) were complicated by cerebral embolism, in 3 patients a pericard tamponade occurred, and in one case caused by transseptal punction of the interatrial septum. The most complications were peripheral vascular problems in 19 patients (4.2%). Predictors for increased risk dur to retrograde catheterization were age > 70 years (p = 0.008) and aortic valve area < or = 0.7 cm2 (p = 0.02). patients with a doppler echocardiographic instantaneous pressure gradient > or = 70 mm Hg were more likely to sustain a complication (p = 0.04). The retrograde catheterization of a stenotic aortic valve was successful in most cases. In approximately 2% of patients, complications occurred which can be attributed directly to retrograde catheterization and with significant higher frequency in patients over 70 years and with severe stenosis. Especially in these cases, invasive determination of the gradient should not be performed if reliable doppler echocardiographic information is available.

Adult↗
PubMed1999

Effect of HMG-CoA reductase inhibitors on extracellular matrix expression in human vascular smooth muscle cells.

Clinical studies have shown that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors can stabilize atherosclerotic plaques and slow their progression. One determinant of plaque stability and size is the composition of the vascular extracellular matrix. The aim of this study was to evaluate the effects of different HMG-CoA reductase inhibitors on the expression of major components of the vascular extracellular matrix in smooth muscle cells. Cultured human vascular smooth muscle cells were incubated for 24-72 h with the HMG-CoA reductase inhibitors lovastatin (1-50 micromol/L), simvastatin (0.05-20 micromol/L), and pravastatin (1-100 micromol/L). RNA expression of the extracellular matrix proteins thrombospondin-1, fibronectin, collagen type I, and biglycan as well as expression of the cytokine TGF-beta1 was determined by Northern blotting. Extracellular matrix protein secretion was visualized by immunofluorescence. In addition, cell proliferation and viability were measured using BrDU-ELISAs, MTT-tests, and direct cell counting. Expression of thrombospondin-1 was significantly decreased after 24 h incubations with lovastatin in concentrations as low as 1 micromol/L. Coincubation with the cholesterol precursor mevalonate completely reversed this effect. The downregulation of thrombospondin-1 expression occured in the same concentration range that also inhibited cell proliferation. In contrast, lovastatin did not affect expression of fibronectin, whereas collagen type I and biglycan expression decreased only after long incubations with high, toxic lovastatin concentrations. Simvastatin, but not the very hydrophilic compound pravastatin, had a similar effect on extracellular matrix expression as lovastatin. In summary, lovastatin and simvastatin predominantly decrease the expression of the glycoprotein thrombospondin-1, which is functionally associated with smooth muscle cell migration and proliferation. In contrast, expression of plaque-stabilizing extracellular proteins such as collagen type I and biglycan are much less affected.

Cell Division↗
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

Extent, determinants and clinical importance of pressure recovery in patients with aortic valve stenosis.

AIMS: In experimental studies the recovery of pressure distal to stenotic valve orifices has been well described. We evaluated the extent, determinants, and clinical importance of pressure recovery in patients with aortic valve stenosis. METHODS AND RESULTS: The study was performed in 37 patients with aortic valve stenosis, in whom cardiac catheterization was performed and left ventricular and aortic pressures were determined using a high-fidelity multi-tip micromanometer catheter. To register the pressure waveforms accurately the catheter was positioned so that the proximal micromanometer was in the left ventricle, the second at the site of minimal pressure in the vena contracta, and the third (the most distal) in the ascending aorta 16 cm further downstream. The amount of pressure recovery within the ascending aorta was up to 44% of the maximal pressure drop. The index pressure recovery was directly correlated to the Gorlin-derived aortic valve area (r=0.80) and indirectly correlated to the ratio of aortic valve area and the cross-sectional area of the ascending aorta. CONCLUSIONS: This clinical study confirmed experimental data, that index pressure recovery is dependent on the ratio of the effective valve area and the cross-sectional area of the ascending aorta. Pressure recovery may need to be considered in patients with mild to moderate aortic stenosis and with a small cross-sectional area of the ascending aorta.

Adult↗