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Biomedical subjects

A Baumbach

Publications and source records attributed to A Baumbach.

At least 37 records · Page 2Linked to original sources
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↗
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↗
PubMed1999

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

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

Angina Pectoris↗
PubMed1999

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

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

Abciximab↗
PubMed1998

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

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

Aged↗
PubMed1998

[Advantages in using intravascular ultrasound in percutaneous transluminal coronary angiography].

UNLABELLED: Recent randomized clinical trials reported a reduction of restenosis using intracoronary stents and suggested that this restenosis reduction is a result of the higher immediate luminal gain in comparison to conventional percutaneous transluminal coronary angioplasty (PTCA). The hypothesis of this study is based on the assumption that IVUS guided PTCA leads to equivalent long term PTCA results as compared to PTCA and the additional placement of a stent. Thus, the purpose of this non-randomized single center study was to evaluate (1) the safety and efficacy and (2) the long term outcome of vessel size adapted PTCA in patients with native coronary lesions. From April 1995 to March 1996 the morphological dimensions of the target lesions were determined in 107 patients with 108 lesions by intravascular ultrasound prior to conventional balloon angioplasty. Quantitative parameters of the vascular dimensions were assessed on-line and the diameter of the balloon catheter was adapted to the external elastic membrane (EEM) at the lesion site minus 10%. Using this strategy, mean balloon diameter was 4.1 +/- 0.5 mm. Acute and one year clinical follow-up results were obtained in all 107 patients. Angiographic success was defined as a final percent diameter stenosis of < 30%. The following criteria determined by postinterventional IVUS were also used to define a successful PTCA: luminal CSA gain of > 30% with an angiographically patent flow (TIMI 3). Acute events occurred in two patients (one death and one successful acute surgical revascularisation). During one year follow-up, 11 patients had a clinical event including death, Q-wave MI, surgical revascularisation, and repeat PTCA. In 83 patients (78%), control angiography was performed and revealed an angiographic restenosis rate of 21% using the NHLBI criterion of a diameter stenosis > 50% CONCLUSION: The use of balloon diameters following these measurements is safe in the acute setting with a low number of in hospital events and effective in reducing clinical events as well as angiographic restenosis rates during one year follow-up. These promising results warrant verification in larger scale randomized trials.

Aged↗
PubMed1998

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

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

Administration, Cutaneous↗
PubMed1998

Acute and one year follow-up results after vessel size adapted PTCA using intracoronary ultrasound.

AIMS: Recent randomized clinical trials have reported a reduction in restenosis with intracoronary stents and have suggested that this restenosis reduction is a result of the higher immediate luminal gain, in comparison to conventional percutaneous transluminal coronary angioplasty (PTCA). The hypothesis of this study is based on the assumption that PTCA results may be optimized by determining vessel dimensions before intervention, using intravascular ultrasound. This may lead to long-term PTCA results equivalent to PTCA and the additional placement of a stent. The purpose of this prospective non-randomized single-centre study was to evaluate (1) the safety and efficacy and (2) the long-term outcome of vessel-size adapted PTCA in patients with native coronary artery obstructions. METHODS AND RESULTS: From January 1995 to December 1995 the morphological dimensions of target lesions were determined in 144 patients with 152 lesions by intravascular ultrasound prior to conventional balloon angioplasty. Quantitative assessment of the vascular dimensions were assessed on-line and the diameter of the balloon catheter was adapted to the external elastic membrane diameter at the lesion site. Using this strategy, mean balloon diameter was 4.0 +/- 0.5 mm and mean pressure for complete balloon expansion was 7 +/- 2 atmospheres. Acute and one year follow-up results were obtained in all 144 patients. Acute events occurred in two patients (one death and one acute surgical revascularization). During one year follow-up, 16 patients (12%) had a clinical event including one cardiac death, two transmural myocardial infarctions, 10 repeat PTCAs within the target lesion and three elective coronary artery bypass grafts (CABG). In 75% (n:112) control angiography was performed and revealed an angiographic restenosis rate of 21% using the NHLBI criteria of a diameter stenosis > 50%. CONCLUSION: Intravascular ultrasound provides an accurate and precise description of vascular dimensions at the site of the stenotic lesion. The use of balloon diameters following these measurements appears to be (1) safe in the acute setting with a low number of in hospital events and (2) gives a low restenosis rate and number of clinical events at one year follow-up. These promising results warrant verification in larger-scale randomized trials.

Aged↗
PubMed1998

Lesion morphology assessed by pre-interventional intravascular ultrasound does not predict the incidence of severe coronary artery dissections.

AIMS: Coronary artery dissections are common findings following percutaneous transluminal coronary angioplasty and occur with an incidence of approximately 20% to 40%. The purpose of this study was to evaluate the impact of intravascular ultrasound for the prediction of severe dissections by pre-interventional analysis of lesion morphology and plaque composition. METHODS AND RESULTS: Pre- and post-interventional intravascular ultrasound was performed in 197 patients with 205 lesions. Using intravascular ultrasound criteria, 24 lesions were classified as soft (hypo- or iso-echogenic), 73 as intermediate (hyper-echogenic) and 108 as calcified (calcific arc > 90 degree of the vessel circumference). Additionally, calcium localization was defined as subendothelial, central or deep. The incidence of dissections was 37.5% in patients with soft lesions, 24.7% in patients with intermediate and 36.1% in patients with calcified lesions. In calcified lesions, the occurrence of severe dissections was not dependent on the localization of calcium deposits. The procedural parameters were similar in all patients. The minimal inflation pressure, however, was significantly higher in calcified lesions (P < 0.01). CONCLUSION: Assessment of lesion morphology by intravascular ultrasound cannot predict the occurrence of severe dissections following percutaneous transluminal coronary angioplasty. Furthermore, despite significantly higher inflation pressures in heavily calcified lesions, the incidence of dissections was found to be comparable in all lesions.

Adult↗