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Biomedical subjects

K R Karsch

Publications and source records attributed to K R Karsch.

At least 55 records · Page 3Linked to original sources
PubMed1999

Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study.

OBJECTIVES: We investigated the association between insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene, the presence and extent of coronary artery disease, and myocardial infarction. BACKGROUND: The D allele of the ACE gene has been associated with coronary artery disease and myocardial infarction, but this association has been challenged in epidemiological studies. METHODS: Nine hundred and sixty-nine men and 341 women undergoing coronary angiography were studied. The ACE genotypes were assessed by polymerase chain reaction from genomic deoxyribonucleic acid, homozygosity for the D allele was controlled using an insertion-specific primer. Coronary artery disease was defined by angiographic criteria, the extent of coronary artery disease by the number of coronary arteries with >/=50% lumen narrowing. RESULTS: The ACE genotypes did not differ in terms of age, sex, body mass index, blood pressure, plasma lipids or lipoproteins. We found no association between the ACE genotypes and coronary artery disease (odds ratio, 95% confidence interval in DD genotypes for coronary artery disease in men 0.97, 0.70-1.36; in women 1.56, 0.95-2.57), extent of coronary artery disease (men 1.17, 0.85-1.61; women 1.24, 0.65-2.34), or myocardial infarction among the patients with coronary artery disease (men 1.07, 0.78-1.48; women 0.95, 0.50-1.76). The ACE genotype was not associated with coronary artery disease or myocardial infarction in hypertensives (n=771; odds ratio for coronary artery disease 0.93, 0.65-1.34; odds ratio for myocardial infarction 0.94, 0.66-1.33), or in patients </=60 years (n=649; odds ratio for coronary artery disease 1.05, 0.72-1.52; odds ratio for myocardial infarction 0.96, 0.63-1.47). CONCLUSION: ACE insertion/deletion gene polymorphism is associated neither with the prevalence nor the extent of coronary artery disease, nor with myocardial infarction in this relatively large sample of Caucasian men and women. Genotyping for ACE insertion/deletion polymorphism is not useful in assessing the individual risk of coronary artery disease or myocardial infarction.

Age Factors↗
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↗
PubMed1999

Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes.

Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic gene polymorphism at codon 192 (glutamine/arginine) has been associated with coronary artery disease (CAD). To further evaluate the role of this paraoxonase gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase genotype in 288 type 2 diabetic patients (170 with and 118 without angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was assessed using polymerase chain reaction followed by AlwI digestion. The frequency of the Gln allele was 0.656 in the CAD patients and 0.746 in the controls (chi2 = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age-adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects carrying at least one Arg allele. In the multivariate analysis, this association was even stronger after correction for the possible confounders age, sex, smoking history, and hypertension. Among current and former smokers, the odds ratio (OR) for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P < 0.01). The paraoxonase Arg allele was not associated with the history of myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not myocardial infarction in type 2 diabetic patients, a risk factor further modified by cigarette smoking. This risk could possibly be explained by a reduced ability of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.

Arginine↗
PubMed1998

Accuracy of computer-based quantification of aortic valve stenosis.

In patients with aortic valve stenosis, the quantification of stenosis is usually performed using fluid-filled catheters and a computerized calculation program. The aim of this study was to determine the accuracy of this technique in comparison to the manual planimetry of the area between the curves of a simultaneous registration, using a multitip micromanometer catheter. The study was performed in 19 patients, in whom left and right heart catheterization was warranted. Systolic left ventricular and aortic peak pressures were significantly overestimated using a fluid-filled catheter (206 +/- 35 vs. 199 +/- 37 mm Hg, P = 0.0003, and 148 +/- 18 vs. 143 +/- 21 mm Hg, P = 0.0052). However, peak-to-peak pressure gradients were identical comparing both techniques (58 +/- 31 vs. 56 +/- 32 mm Hg, r = 0.983). The mean pressure gradients and aortic valve areas based on simultaneous measurements of left ventricular and aortic pressures by micromanometer catheters were identical to the values determined by a computer-based program using fluid-filled catheters (54 +/- 21 vs. 52 +/- 21 mm Hg, r = 0.923, P < 0.05, and 0.75 +/- 0.25 vs. 0.77 +/- 0.25 cm2, r = 0.935). Thus, the conventional use of fluid-filled catheters and of a computerized calculation of aortic valve area is valid for quantification of aortic stenosis in patients with sinus rhythm and without significant aortic regurgitation.

Adult↗
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

[The influence of coronary artery dissection on long-term outcome after percutaneous transluminal coronary angioplasty].

UNLABELLED: The influence of a coronary dissection on long-term outcome after PTCA has been controversely discussed in the past. Whereas diverse experimental studies have shown a positive relation between dissection and the incidence of restenosis, clinical trials could not document an influence of dissection on long-term outcome. However, most of the trials did not distinguish between the different morphologic configuration of the vascular dissection. Thus, the aim of the present study was to determine the influence of dissections on restenosis in regard to their amount and morphologic configuration. The prognostic importance of the National Heart, Lung, and Blood Institute classification on dissection as well as the importance of an additional classification of angiographic complications after PTCA were investigated to determine possible pathophysiologic mechanisms of the restenosis process. The study included 141 consecutive patients with 143 stable dissections after PTCA. A follow-up study was performed 13 months in mean after successful PTCA, which included clinical, symptomatic, and functional aspects of patients. In this patient population, type C dissections (Dorros et al.) showed a relevantly increased risk of a clinical adverse event (41.0%), whereas patients with a type A dissection had only a small risk of an adverse event (10.0%) over the investigation period. Type B dissections revealed an intermediate risk (18.0%), and type D dissections showed a risk of 33.3% of an adverse event, which was lower than that observed for type C dissections. The AC-classification of the postinterventional coronary morphology was a stronger predictor of an adverse outcome after PTCA (p = 0.0003) than was the Dorros-classification (p = 0.0056). CONCLUSION: The grade of a coronary dissection was highly, positively related to an ischemic event after PTCA using both the Dorros and the AC-classification (p = 0.0056/p = 0.0003). In regard to the special association of the AC-class with the amount of vascular injury, we conclude that the amount and configuration of coronary dissection correlates with the long-term outcome after PTCA.

Aortic Dissection↗
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

Downregulation of beta-adrenergic receptors by low density lipoproteins and its prevention by beta-adrenergic receptor antagonists.

OBJECTIVE: Vasodilation by beta-adrenergic receptors of smooth muscle cells appears to be impaired early after the onset of hypercholesteremia. The aim of this study was to analyze the modulation of beta-adrenergic receptor density and adenylyl cyclase activity in the presence of moderately elevated concentrations of LDL. The effects of beta 1- and beta 2-adrenergic receptor antagonists on LDL-induced receptor changes were studied. METHODS AND RESULTS: Media explants of porcine coronary arteries were incubated with moderately elevated LDL concentrations (0.7-3.9 mmol/l). The density of beta-adrenergic receptors was determined in plasma membranes using the radioligand [125I]iodocyanopinodolol. LDL (3.9 mmol/l) resulted in a decrease of beta-adrenergic receptor density (control 137 +/- 5 vs. 89 +/- 7 fmol/mg protein, P < 0.01). After removal of LDL and cultivation for an additional 3 days beta-adrenergic receptors increased to 129 +/- 5 fmol/mg. In the presence of the beta 1- or beta 2-adrenergic receptor antagonists the LDL-mediated decrease was inhibited. Addition of metoprolol after 3 days of LDL incubation caused a restoration of receptor density. The basal, isoproterenol- and forskolin-stimulated adenylyl cyclase activities were increased after LDL incubation by 180, 110 or 80%, respectively. CONCLUSION: Moderately elevated LDL levels decreased beta-adrenergic receptor density while adenylyl cyclase activity was simultaneously increased. beta 1- or beta 2-adrenergic receptor antagonists prevented this receptor decrease and might preserve the beta-adrenergic receptor density in the presence of moderately elevated LDL levels.

Adenylyl Cyclases↗
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

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is associated with coronary artery plaque calcification as assessed by intravascular ultrasound.

OBJECTIVES: We evaluated the influence of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene on coronary plaque morphology and calcification in patients with angiographically documented coronary artery disease (CAD). BACKGROUND: The ACE I/D polymorphism has been associated with an increased risk of myocardial infarction in patients with the DD genotype but not with the presence of native CAD. METHODS: We studied 146 patients undergoing percutaneous transluminal coronary angioplasty for stable angina pectoris by means of preinterventional intravascular ultrasound (IVUS). Qualitative and quantitative criteria were used to classify the target lesions as poorly or highly echoreflective or as calcified. Genomic deoxyribonucleic acid was analyzed by polymerase chain reaction (PCR) to identify the I/D polymorphism, with a second insertion-specific PCR in DD genotypes to prevent mistyping. RESULTS: The ACE genotype groups (DD 46, ID 68, II 32) were well matched for the basic characteristics. Patients with the DD genotype had significantly more calcified lesions (DD 80%, ID 57%, II 66%; unadjusted odds ratio [OR] 2.88, 95% confidence interval [CI] 1.30 to 6.92, p = 0.008) and more calcifications >180 degrees of the vessel circumference (DD 22%, ID 10%, II 6%; OR 2.80, 95% CI 1.05 to 7.63, p = 0.03). The prevalence of myocardial infarction was not significantly associated with coronary calcification (OR 1.44, 95% CI 0.72 to 2.88, p = 0.31). CONCLUSIONS: Patients with CAD and the ACE DD genotype have a significantly higher incidence and greater extent of coronary lesion calcification, as determined by IVUS. This finding indicates that the ACE I/D gene polymorphism is related to the development or progression of atherosclerotic plaque calcification.

Aged↗
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↗
PubMed1998

Incidence, outcome and prediction of early clinical events following percutaneous transluminal coronary angioplasty. A comparison between treatment with reviparin and unfractionated heparin/placebo (results of a substudy of the REDUCE trial).

BACKGROUND: Unfractionated heparin and its low molecular weight fragments possess antithrombotic properties, properties that are routinely exploited in coronary angioplasty (PTCA). OBJECTIVES: In the setting of the REDUCE trial, a randomized, double-blind, multicentre trial, the occurrence of acute or early clinical events was compared in patients treated with either unfractionated heparin/placebo or low molecular weight heparin (reviparin). METHODS AND RESULTS: Six hundred and twelve patients with native coronary artery obstructions randomized between unfractionated heparin/placebo and reviparin, were analysed. Baseline characteristics were similar in both groups. Using the intention-to-treat analysis, major acute or early events (myocardial infarction, re-PTCA, bypass surgery, death) occurred in 42 patients (7%), 29 in the control group and 13 in the treatment group (P=0.027). In order to develop a predictive model for the risk of early events following coronary balloon angioplasty, clinical as well as pre-PTCA and procedural characteristics were analysed. Thrombi at the treated lesion site (P=0.02), dissection (P<0.001), lesion type B2 and C according to the NHLBI classification (P<0.001), diameter stenosis >50% post-PTCA (P<0.001), and length of stenosis >20mm (P=0.005) were significantly associated with the occurrence of acute events. By multiple logistic regression analysis, in which these variables and the treatment regimen were entered, dissection (P=0.042), diameter stenosis >50% (P<0.028) and lesion type B2 and C (P=0.017) were found to be independently predictive of early adverse events. Bleeding complications were similar in the two treatment groups. CONCLUSIONS: Reviparin, given in a very early stage of vascular injury, compares favourably with unfractionated heparin/placebo, by reducing abrupt closure and acute-phase adverse outcome following PTCA. With respect to the evaluated risk factors for acute events, the positive effect of reviparin on early adverse outcome after PTCA may be due to improved antithrombotic properties as compared to unfractionated heparin.

Angina Pectoris↗
PubMed1998

Dynamic regulation of beta-adrenergic receptors by endothelin-1 in smooth-muscle cells.

Elevated endothelin-1 (ET-1) levels are found in atherosclerosis, myocardial ischemia, and heart failure, and are correlated with increased mortality rates. Contrary to expectations, elevations of endogenous ET-1 levels in transgenic mice are not associated with increases in arterial blood pressure or with vasospasm, although these effects can be observed after i.v. ET-1 administration. The aim of this study was to determine the regulatory effects of ET-1 on the expression of vasodilator beta-adrenergic receptors and their ability to activate adenylyl cyclase. Smooth-muscle cells were incubated with ET-1 (10(-7) mol/L) for 3 days. The density of ET-1 or beta-adrenergic receptor binding sites was determined using a radioligand binding procedure. Adenylyl cyclase activity was measured to assess any functional changes in the beta-adrenergic receptor density. ET-1 incubation reduced ET-1 binding sites by 70%. In contrast, the beta-adrenergic receptor density increased from 354 +/- 35 to 538 +/- 50 fmol/mg protein (p < 0.01; n = 7) after 3 days. ET-1 increased beta-adrenergic receptors dose-dependently. Incubation with ET-1 for different periods of time showed an initial decrease of 30% after 6 h of ET-1 incubation. However, after 24 h ET-1 induced an increase of beta-adrenergic receptors, reaching a maximal amount after 48 h. An increased stimulation of beta-adrenergic receptor-activated adenylyl cyclase was observed after 3-day ET-1 incubation compared to controls. These data demonstrate that chronic ET receptor activation by ET-1 results in a functionally significant increase in beta-adrenergic receptor density and adenylyl cyclase activity.

Adenylyl Cyclases↗
PubMed1998

Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease.

OBJECTIVE: Flow associated dilatation (FAD%) and intimal media thickness are established markers of early atherosclerosis. This study aimed to compare the ability of the non-invasive measurements FAD% and intimal media thickness to predict coronary artery disease. METHODS: FAD% and intimal media thickness were determined using high resolution ultrasound in 122 patients with clinically suspected coronary artery disease before coronary angiography. Results are given as mean (SD). RESULTS: Patients with coronary artery disease had reduced FAD% compared with those with angiographically normal coronary vessels (3.7 (4.1) v 7.0 (3.5)%, p < 0.001), whereas intimal media thickness tended to be increased in patients with coronary artery disease (0.58 (0.35) v 0.47 (0.11)mm, p = 0.054). There was a negative correlation between FAD% and intimal media thickness (R = -0.317, p = 0.0004). Receiver operating characteristic analysis showed that FAD% < or = 4.5% predicted coronary artery disease with a sensitivity of 0.71 (95% confidence interval 0.61 to 0.80) and a specificity of 0.81 (0.58 to 0.95). In contrast, intimal media thickness showed a positive correlation with the extent of coronary artery disease (number of vessels with a lesion > or = 50%) (R = 0.324, p = 0.0003), without a clear cut off point. CONCLUSIONS: In patients with clinically suspected coronary artery disease, FAD% discriminates between the presence or absence of coronary artery disease, whereas intimal media thickness is associated more with the extent of coronary artery disease.

Adult↗
PubMed1997

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

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

Animals↗