Publications (10)10.04 Total impact
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Article: Effects of gold coating of coronary stents on neointimal proliferation following stent implantation.
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ABSTRACT: Experimental studies suggest a reduced neointimal tissue proliferation in vascular stainless steel stents coated with gold. This prospective multicenter trial evaluated the impact of gold coating on neointimal tissue proliferation in patients undergoing elective stent implantation. The primary end point was the in-stent tissue proliferation measured by intravascular ultrasound at 6 months comparing stents of identical design with or without gold coating (Inflow). Two hundred four patients were randomized to receive uncoated (group A, n = 101) or coated (group B, n = 103) stents. Baseline parameters did not differ between the groups. Stent length and balloon size were comparable, whereas inflation pressure was slightly higher in group A (14 +/- 3 vs 13 +/- 3 atm, p = 0.013). Procedural success was similar (A, 97%; B, 96%). The acute angiographic result was better for group B (remaining stenosis 4 +/- 12% vs 10 +/- 11%, p = 0.002). Six-month examinations revealed more neointimal proliferation in group B. By ultrasound, the neointimal volume within the stent was 47 +/- 25 versus 41 +/- 23 mm(3) (p = 0.04), with a ratio of neointimal volume-to-stent volume of 0.45 +/- 0.12 versus 0.40 +/- 0.12 (p = 0.003). The angiographic minimal luminal diameter was smaller in group B (1.47 +/- 0.57 vs 1.69 +/- 0.70 mm, p = 0.04), with a higher late luminal loss of 1.17 +/- 0.51 versus 0.82 +/- 0.56 mm (p = 0.001). Thus, gold coating of the tested stent type resulted in more neointimal tissue proliferation.The American Journal of Cardiology 05/2002; 89(7):801-5. · 3.37 Impact Factor -
Article: Experimental diabetes and left ventricular hypertrophy: effects of beta-receptor blockade.
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ABSTRACT: Left ventricular hypertrophy involves growth of cardiomyocytes, as well as remodeling of extracellular matrix proteins (ECMPs). Several metabolic abnormalities may be triggered secondary to hyperglycemia in diabetes. The effects of combined supravalvular aortic banding and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of these two conditions. Moreover, this study focused on the impact of beta-adrenoceptor blockade with carvedilol (C) on the expression of ECMPs. Sixty male Wistar rats were allocated to six groups: control (CON), CON+C, streptozotocin (65 mg/kg iv)-induced diabetes (D), D+C, aortic stenosis (AS)+D and AS+D+C. Follow-up was 6 weeks. Relative left ventricular weight was elevated and body weight was decreased in D, AS+D and AS+D+C rats (P<.05 vs. CON). Diabetes elevated cardiomyocyte widths, perivascular/interstitial fibrosis (P<.01 each), as well as ECMPs: collagen I/fibronectin/laminin were 3.4-fold/4.1-fold/1.5-fold elevated in D rats and further increased (4.6-fold/5.9-fold/1.9-fold) in AS+D rats (P<.01 vs. CON). Heart rate and blood pressure decreased in D and AS+D rats (P<.05 vs. CON). Carvedilol application attenuated the overexpression of ECMPs. Beta-adrenoceptor blockade results in regression of the hypertrophic phenotype and in decrease of ECMP in rats with experimental diabetes and in animals with combined chronic pressure overload and hyperglycemia. These results represent a new mechanism of carvedilol that may contribute to the observed beneficial effects in heart failure.Cardiovascular Pathology 11(4):229-37. · 2.07 Impact Factor -
Article: Effects of aortic stenosis on renal renin, angiotensin receptor, endothelin and NOS gene expression in rats.
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ABSTRACT: Published data regarding the effects of common cardiovascular diseases, i.e. aortic stenosis on renal regulation of major vasoconstrictive (renin, endothelins) and vasodilatory systems (NO) are controversial. Therefore we aimed to evaluate the effects of chronic aortic stenosis on the renal renin-angiotensin, endothelin and NO systems. Experimental supravalvular aortic stenosis was induced by using silver clips with a 0.6 mm internal diameter on the ascending aorta of weanling rats. Renal endothelin-1 (ET-1), endothelin-3 (ET-3), renin, AT(1a), AT(1b), eNOS, and bNOS gene expression were assessed by RNase protection assay. Renal renin gene expression increased twofold in rats with aortic stenosis. In contrast, renal ET-1, ET-3, eNOS, bNOS, and AT(1a), AT(1b) gene expression were unchanged in rats with aortic stenosis. Our study demonstrates that in rats with severe experimental supravalvular aortic stenosis only renal renin gene expression is stimulated. This contrasts with severe heart failure where endothelins and NO synthases are also upregulated. Different patterns of regulation of renal vasoactive mediators may be of importance for the extent of the renal impairment associated with aortic stenosis, and may be correlated with the severity of congestive heart failure.American Journal of Nephrology 22(1):84-9. · 2.54 Impact Factor -
Article: Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats.
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ABSTRACT: Heart failure is known to be a complication of insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) even in the absence of coronary heart disease or hypertension. The mechanisms leading to diabetic cardiomyopathy are unknown. The aim of the study was to characterize structural and functional alterations in hyperinsulinemic Zucker diabetic fatty (ZDF) rats treated with or without insulin. Diabetic animals showed a twofold increase in cardiomyocyte volume with increased left ventricular ANP but not BNP mRNA levels in spite of a reduced plasma renin activity (PRA) 2 months after onset of diabetes compared to nondiabetic littermates. These changes were associated with an increase in left ventricular performance as assessed by echocardiography. Insulin treatment led to a significant increase in body weight (BW), total heart weight, myocardial protein content, and left ventricular mass (LVM). Perivascular fibrosis and laminin thickness were significantly augmented in diabetic rat myocardium irrespective of insulin treatment, whereas interstitial collagen I and fibronectin were similarly found in diabetic and control myocardium. Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy and enhanced cardiac contractility. It is suggested that hyperinsulinemia may be involved in cardiac hypertrophy.Cardiovascular Pathology 13(1):11-9. · 2.07 Impact Factor -
Article: Effects of Beta-Receptor Blockade and Angiotensin II Type I Receptor Antagonism in Isoproterenol - Induced Heart Failure in the Rat
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ABSTRACT: The aim of this study was to examine the effects of both angiotensin II type I receptor antagonism using losartan (LOS) and beta-receptor blockade by metoprolol (MP) in isoproterenol-induced cardiac injury in the rat. Two weeks after isoproterenol (ISO) application, 90 ISO and 30 control (CTRL) rats were examined. ISO rats were treated for two weeks with either LOS, MP, or vehicle (n = 30 each group). Compared to CTRL, ISO induced left ventricular hypertrophy (LVH), fibrosis, and overexpression of extracellular matrix proteins. LOS significantly attenuated these changes. MP only reduced LVH, but exerted no effect on structural alterations. LV end-diastolic and mean right atrial pressures were significantly increased in the ISO group and normalized in the LOS and MP group. Mean aortic blood flow velocity was significantly decreased in the ISO group and unaltered in the LOS and MP group versus CTRL. Blood pressure was decreased in ISO and LOS rats. MP treatment had no effect on blood pressure, but significantly lowered heart rate. Isoproterenol induced mild heart failure. Losartan and metoprolol applications in ISO-treated rats were highly effective in attenuating hemodynamic alterations and LVH. Early application of losartan 24 hours after isoproterenol-induced cardiac injury revealed significant beneficial effects on myocardial structure.Cardiovascular Pathology. -
Article: Growth hormone and interstitial fibrosis
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Article: Development of heart failure following isoproterenol administration in the rat: role of the renin-angiotensin system
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ABSTRACT: Objective : High dosages of catecholamines induce cardiomyocyte necrosis and interstitial fibrosis in rats. We investigated whether this initial damage is followed by the development of heart failure and assessed the particular role of the renin–angiotensin system using ramipril. Methods and Results : Following the administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol+ramipril. Isoproterenol induced significant increases of echocardiographically measured left ventricular end-diastolic posterior wall thickness and dimension, whereas ramipril treatment significantly attenuated these changes. Left ventricular end-diastolic pressure was markedly increased in isoproterenol-treated rats and normalized following ramipril. Isoproterenol rats were further characterized by hormonal activations including transient elevations of plasma renin activity, aldosterone and cardiac angiotensin converting enzyme activity. Histomorphological characterization of isoproterenol-treated hearts demonstrated cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly reduced the amount of necrosis as well as the expression of extracellular matrix proteins. Conclusions : In rats, a toxic dosage of isoproterenol caused characteristic myocardial damage that subsequently resulted in mild heart failure. Ramipril administration following isoproterenol was highly effective to attenuate hemodynamic and hormonal alterations as well as the development of left ventricular hypertrophy, but had only little influence on the expression of extracellular matrix proteins. Since angiotensin converting enzyme inhibition had no impact on the initial myocardial injury, the development of heart failure in this model seems to require functional integrity of the renin–angiotensin system. -
Article: Effects of growth hormone on renal renin gene expression in normal rats and rats with myocardial infarction
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ABSTRACT: Background. Published data regarding effects of growth hormone (GH) on the renin system are controversial. The aim of this study therefore was to evaluate the effects of GH on the renin system in normal rats and rats with myocardial infarction (MI). Methods. Normal rats received 2, 5, or 10 IU GH/kg/day or vehicle subcutaneously for 4 weeks. Furthermore rats with MI were randomized to receive 2 IU GH/kg/day or vehicle for 4 weeks. Subdivision into MI groups (mild, moderate, and large) was by histological determination of infarct size. Renal renin gene expression was assessed by RNAase protection assay and plasma renin activity by radioimmunoassay. In addition, isolated mouse juxtaglomerular cells were exposed to GH for 20 h, and renin secretion rates were assessed. Results. GH treatment in normal rats for 4 weeks increased body weight, and kidney weight to body weight ratio, but did not affect renin secretion and renal renin gene expression. In rats with large MI, renal renin gene expression increased about fourfold, but was unchanged in rats with small and moderate MI as compared to normal rats. In rats with MI, body weight decreased and this decrease was partially reversed by GH treatment. GH treatment did not change renal renin gene expression, and renin secretion in rats with MI. Renin secretion of isolated juxtaglomerular cells was unaffected by GH. Conclusions. Our study demonstrates that GH treatment has no significant effect on renin secretion and on renal renin gene expression in normal rats and in rats with stimulated renin system due to MI in vivo. In isolated juxtaglomerular cells in vitro , renin secretion was also unaffected by GH. -
Article: Extracellular Matrix Proteins in Cardiac Fibroblasts Derived from Rat Hearts with Chronic Pressure Overload: Effects of Beta-receptor Blockade
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ABSTRACT: Left ventricular hypertrophy (LVH) is accompanied by progressive accumulations of extracellular matrix proteins. They are produced predominantly by cardiac fibroblasts that surround the cardiac myocytes. The aim of this study was to emphasize the role of a combined approach using both in vivo and in vitro studies to elucidate the effects of carvedilol on cardiac remodeling. We therefore used an established model of supravalvular aortic banding and cardiac fibroblasts. LVH was induced by banding of the ascending aorta. Male Wistar rats were allocated to four groups: sham-operated, sham+carvedilol, aortic stenosis (AS), and AS+carvedilol. Treatment time was four weeks. Fibroblasts were isolated from the entire left ventricle of sham and AS rats. Carvedilol/metoprolol/prazosin were added (0.1, 1.0 and 10μ ; 24 h). In addition, interferon- γ was applied for 24 h (10, 100 and 1000 IU). AS rats revealed increased LV weights (+27%) and cardiomyocyte widths as compared to sham-operated rats (1.6-fold,P <0.01). Carvedilol reduced LVH by 20%. This finding was accompanied by a decrease of laminin, fibronectin, collagen I and III in vivo. Collagen I/III and fibronectin were increased in fibroblasts of AS v sham rats (P<0.0001, each). Carvedilol reduced collagen I, III and fibronectin by 40/60/35% (0.1 μP<0.001) irrespective of LVH. Carvedilol had no effects on collagen IV and laminin. Carvedilol dose-dependently reduced the proliferation rate by 20% at 0.1 μ (P<0.0001). Metoprolol and prazosin had no effect on the expression of extracellular matrix proteins and on the proliferation of the cells of either origin. Interferon- γ blunted the proliferation rate of cultured fibroblasts and lead to a significant decrease in extracellular matrix deposits. These results indicate that the effects of carvedilol may be due to the antiproliferative or antioxidative properties of this unselective beta-adrenergic receptor antagonist. These changes of the extracellular matrix represent a new mechanism of carvedilol that may contribute to the observed beneficial effects in congestive heart failure.Journal of Molecular and Cellular Cardiology. -
Article: Systemic vasoconstriction induced by inhibition of nitric oxide synthesis is attenuated in conscious dogs with heart failure
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ABSTRACT: Study objective – The aim was to test the hypothesis that endothelium dependent vasomotor control is impaired in heart failure. Design and subjects – The haemodynamic effects of NG-nitro-L-arginine (NNA), an inhibitor of nitric oxide synthesis, were studied in five dogs with and without pacing induced heart failure. Main results – In healthy dogs, NNA increased total peripheral resistance and arterial pressure, decreasing cardiac output and heart rate. These effects were partially reversed by L-arginine. In dogs with heart failure, NNA did not change any haemodynamic variable. However, L-arginine decreased total peripheral resistance. Conclusions – These findings support a physiological role for endothelium derived nitric oxide in control of vascular resistance and are in agreement with the hypothesis that endothelium dependent vasomotion may be impaired in heart failure.
