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Biomedical subjects

J Niebauer

Publications and source records attributed to J Niebauer.

At least 19 recordsLinked to original sources
PubMed2006

[Peri-interventional risk in 1,384 cardiac catheterizations in patients aged 80 years or older].

BACKGROUND AND OBJECTIVE: Because of the rising life expectancy in the industrialized countries, ever more cardiac catheterizations are performed in patients aged 80 years or older. Little is known about the incidence of peri-interventional events in this age group. PATIENTS AND METHODS: Between January 1996 and September 2000, a total of 1,085 patients of that age (mean 82.6 +/- 2.6 years) underwent cardiac catheterization and intervention (3% of a total of 43,517 cardiac catheterizations). RESULTS: 827 patients (77%) had significant coronary artery stenoses. 373 of them (45%) were treated with balloon angioplasty, with or without stenting, and 331 (40%) underwent aortocoronary bypass procedures. 31 patients died while in hospital, 17 of them having been in cardiogenic shock on admission. Peri-interventional events, including damage to artery at the site of catheter entry occurred in 2.1% of patients undergoing diagnostic cardiac catheterization and in 11.6% in connection with a percutaneous interventional procedure. CONCLUSION: Both cardiac catheterization and interventional procedures can be done with a justifiable risk in patients aged 80 years or older. These cardiac investigations/interventions should not be withheld in this group of patients for reasons of age.

Age Factors↗
PubMed2005

Euro heart failure survey. Medical treatment not in line with current guidelines.

UNLABELLED: It was the aim of the Euro Heart Survey on Heart Failure to assess whether patients are being treated according to current guidelines. METHODS: In Germany, patients were screened in 7 medical centers if their discharge diagnoses were myocardial infarction, a new episode of atrial fibrillation, or diabetes mellitus. Patients were enrolled if at least one additional criterion was fulfilled: (1) clinical diagnosis of heart failure, (2) hospital admission due to heart failure within the last 3 years, (3) therapy with loop diuretic, (4) medication for heart failure or ventricular dysfunction documented by echocardiography within the past 24 hours prior to death. RESULTS: 2166 patients were screened of whom 747 were included in the study (478 men, 269 women). 93% of the patients suffered from heart failure. Despite the high number of patients with known heart failure (ischemic heart failure in 71%), only 72% received ACE inhibitors and 62% beta-blockers. Average daily dose met recommendations in only 63% of patients on ACE inhibitors and 54% on beta-blockers. 74% of the patients received diuretics (furosemide 36%, thiazide 34%, spironolactone 17%). CONCLUSION: An inadequately low number of patients with heart failure receives medical therapy according to guidelines, despite all the overwhelming evidence for improved morbidity and mortality. Awareness of physicians needs to be improved.

Adrenergic beta-Antagonists↗
PubMed2004

[Therapeutic options in patients with diabetes mellitus type 2 and coronary artery disease: intensified secondary prevention versus percutaneous or surgical revascularization].

Diabetes mellitus is a major risk factor for coronary artery disease and is associated with accelerated disease progression and adverse prognosis. Although relief of symptoms can quickly be obtained by percutaneous intervention or bypass surgery, it does not change patients' prognoses, with the exception of stenoses of the left main stem or left anterior descending artery. A multifactorial intervention, which consists of a low-fat diet, glucose and arterial blood pressure control, smoking cessation and regular physical exercise, emerges as an alternative strategy since it leads to improvement of the modifiable risk factors, exercise tolerance and quality of life.

Angioplasty, Balloon, Coronary↗
PubMed2001

[Statins do not prevent restenosis after coronary angioplasty: where to go from here?].

BACKGROUND: Despite the use of intracoronary stents, approximately 15-20% of patients who undergo percutaneous transluminal coronary angioplasty (PTCA) experience symptomatic restenosis. Known mechanisms of restenotic lesion formation are smooth muscle cell proliferation, extracellular matrix production, remodeling and decreased programmed cell death (apoptosis). RESULTS AND STUDIES: Experimental observations suggest that HMG-CoA reductase inhibitors ("statins") reduce the risk of restenosis. The activity of statins limits the rate of synthesis, not only of cholesterol, but also of a range of other molecules involved in cellular function. Their benefits in primary and secondary prevention of atherosclerosis have been widely recognized. Clinical trials using different types of statins were designed to evaluate their ability to influence the incidence of restenosis after successful conventional PTCA. The results clearly demonstrated that statins reduce lipid levels but do not prevent restenosis. Experimental evidence has failed to translate into clinical effect. The underlying pathological reasons for this shortcoming as well as promising alternative approaches including vascular gene therapy and brachytherapy will be discussed in this review.

Angioplasty, Balloon, Coronary↗
PubMed2001

[The anti-atherogenic mechanism of action of physical training in patients with coronary heart disease].

In randomized trials, moderate to aggressive lipid-lowering therapy as well as regular physical exercise have both been shown to restore endothelial function, slow progression and in some patients even lead to regression of coronary artery disease. Furthermore, a reduced rate of cardiac events, morbidity and mortality have been documented. Similarly, regular physical exercise training has been identified to contribute independently to beneficial changes in the risk factor profile, retardation of the progression of coronary lesions and has been associated with a reduced rate of mortality. Therefore, besides adhering to a low fat diet, patients with coronary artery disease should further be motivated to include physical exercise in their daily routine. Although it has been puzzling how exercise training exerts antiatherogenic effects, accumulating evidence has recently unraveled some of the underlying cellular and molecular pathomechanisms, which will be discussed in this review.

Combined Modality Therapy↗
PubMed2001

Cholesterol-induced upregulation of angiotensin II and its effects on monocyte-endothelial interaction and superoxide production.

Atherogenesis involves an early endothelial dysfunction hallmarked by elevated free radical production and increased adhesiveness for monocytes. It was hypothesized that activation of the tissue renin angiotensin system may contribute to the endothelial alteration. To test this hypothesis, thoracic aortae were isolated from normocholesterolemic (NC; n = 6) and hypercholesterolemic (HC; n = 6; diet: 0.5% cholesterol; 6 weeks) New Zealand white rabbits, and incubated for 2 h with the angiotensin II (Ang II) receptor antagonist Sar-1,Ile-8-Ang II, the antioxidant pyrolidine dithiocarbamate (PDTC) and the protein kinase C (PKC) antagonist staurosporin. Superoxide production from aortic segments was measured by lucigenin-enhanced chemiluminescence. In comparison to the normocholesterolemic state, hypercholesterolemia led to a significant increase in superoxide production (221 +/- 44%, p < 0.02); this was reduced by ex vivo treatment of the vessel segment with Ang II-antagonist (to 130 +/- 29%; p < 0.04 vs HC), or PKC-antagonist (to 86 +/- 26%; p < 0.001 vs HC), or PDTC (to 103 +/- 27%; p < 0.02 vs HC). Monocyte-endothelial interaction was assessed by functional binding assay. When compared to normocholesterolemic rabbits, hypercholesterolemia led to a twofold increase in monocyte binding (74 +/- 13 vs 37 +/- 4 monocytoid cells per high power field (m/hpf); p < 0.03). The Ang II-antagonist and the PKC-antagonist led to a normalization of monocyte-endothelial binding (Ang II-antagonist: 37 +/- 9 m/hpf; PKC-antagonist: 41 +/- 17 m/hpf; p < 0.05). In conclusion, these results indicate that hypercholesterolemia activates the tissue renin angiotensin system, which results in an increased endothelial production of superoxide and monocyte adhesiveness. Ang II-antagonist inhibits free radical production and monocyte adhesion through a mechanism which may include PKC.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed2001

Effects of stenting on adjacent vascular distensibility and neointima formation: role of nitric oxide.

Intravascular stents increase long-term patency but their effects on the vascular mechanics of adjacent segments have not been studied. In this study, stents were deployed in the rabbit abdominal aorta after 1 week of normal diet, 1% cholesterol diet or 1% cholesterol diet with L-nitro arginine (L-NA 60 mg/l water). Intravascular ultrasound showed a small distal decrease in vessel distensibility (area/pressure * 100) before stenting. Distensibility was almost abolished by stenting (0.12 +/- 0.01, p < 0.001), but was increased proximal to the stent and decreased distal to the stent both acutely (proximal: 1.18 +/- 0.10 vs distal: 0.65 +/- 0.06, p < 0.001), and at 4 weeks (proximal: 1.05 +/- 0.08 vs distal: 0.37 +/- 0.07, p < 0.001). Nitric oxide (NO) activity was enhanced proximal to and within the stent, and remained constant distal to the stent, (versus control, proximal: 57 +/- 23%, stent: 136 +/- 35%, distal: 2 +/- 12%, p < 0.01). The I/M ratio was significantly higher proximal to and within the stent than in the distal segment (proximal: 0.40 +/- 0.10, stent: 0.37 +/- 0.12, distal: 0.12 +/- 0.11, p < 0.01). NO blockade with L-NA prevented hyperdistensibility proximally, and significantly increased the I/M ratio within the stent and distally (stent: 0.81 +/- 0.19, distal: 0.30 +/- 0.10, p < 0.05) but not proximally (0.38 +/- 0.09). In conclusion, aortic stenting increases proximal vascular distensibility and intimal lesion formation. Nitric oxide blockade augments intimal growth within but not proximal to the stent.

Animals↗
PubMed2000

Plasma cytokine parameters and mortality in patients with chronic heart failure.

BACKGROUND: Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor 1 and 2 (sTNF-R1/sTNF-R2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CHF patients. METHODS AND RESULTS: In 152 CHF patients (age 61+/-1 years, New York Heart Association [NYHA] class 2.6+/-0.1, peak VO(2) 17.3+/-0.6 mL. kg(-1). min(-1), mean+/-SEM) plasma concentrations of immune variables were prospectively assessed. During a mean follow-up of 34 months (>12 months in all patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 months. In univariate analyses, increased total and trimeric TNF-alpha, sTNF-R1, and sTNF-R2 (all P</=0.0001), sCD14 (P=0.0007), and IL-6 (P=0.005) predicted 24-month mortality. With multivariate analysis and receiver operating characteristics, sTNF-R1 emerged among all cytokine parameters as the strongest and most accurate prognosticator in this CHF population, regardless of follow-up duration and independently of NYHA class, peak VO(2), VE/VCO(2) slope, left ventricular ejection fraction, and wasting (P<0.001). The receiver operating characteristic area under the curve for sTNF-R1 was greater than for sTNF-R2 at 6, 12, and 18 months (all P<0.05). CONCLUSIONS: sTNF-R1 was the strongest and most accurate prognosticator, independent of established markers of CHF severity. Assessment of sTNF-R1 may be useful in identifying patients who are at high risk of death and in monitoring patients undergoing anti-TNF-alpha treatment.

Adult↗
PubMed2000

Myocardial ischemia during physical exercise in patients with stable coronary artery disease: predictability and prevention.

AIMS: We assessed whether exercise-induced myocardial ischemia during intensive group exercise sessions can be predicted in patients with coronary artery disease and stable angina pectoris. METHODS AND RESULTS: Twenty-three patients underwent cardiac catheterization, 201-thallium scintigraphy, and exercise testing prior to participation in group training sessions. Heart rates and myocardial ischemia were documented by Holter monitoring. The individual training heart rate was calculated as a percentage of the maximal heart rate achieved during symptom-limited exercise testing. Myocardial ischemia occurred significantly more often during group exercise sessions (15 of 23 patients) than during treadmill testing (4 of 23 patients, P<0.001). Maximal heart rate (145+/-23 vs. 134+/-21 beats/min, P<0.004) and maximal plasma lactate concentrations (6.0+/-2.9 vs. 4.3+/-2.0 mmol/l, P<0.05) were significantly higher than during symptom-limited exercise testing. Ischemic episodes occurred significantly more often during jogging than during competitive ball games or interval training. Myocardial ischemia occurred in patients who exceeded their individual target training heart rates (43 of 44 episodes; P<0.001). Duration of ischemic episodes did not correlate with any marker obtained at the beginning of the study. CONCLUSION: These data demonstrate that routine diagnostic procedures do not sufficiently identify patients at risk for exercise-induced myocardial ischemia. Ischemic events are only effectively prevented by choosing adequate types of exercise and, above all, by the strict adherence to individual target heart rates.

Coronary Angiography↗
PubMed2000

Inflammatory mediators in heart failure.

Cytokines have been identified as a major player in the pathogenesis and the functional status of patients with heart failure. Herein I review studies which are under way to assess the effects of anti-cytokine therapy, where soon we may see treatments directed against bacteria in the bowel, the translocation process, and endotoxin itself, the binding sites of bacterial endotoxin on immune competent cells, or both.

Animals↗
PubMed2000

Prediction of angiographic stabilization/regression of coronary atherosclerosis by a risk factor graph.

BACKGROUND: The only reason for treating dyslipidaemia is the prevention and/or stabilization of atherosclerosis. Angiographic stabilization/reversal of coronary atherosclerosis predicts a decrease in future atherosclerotic disease manifestations. METHODS: This paper reports on an analysis of eight angiographic trials that use therapy of dyslipidaemia in order to stabilize/reverse coronary atherosclerosis. The analysis involved plotting trial lipid and blood pressure end-points on a risk factor graph which contained a threshold line in order to determine whether bringing trial end-points below that threshold line predicted angiographic stabilization/regression of coronary atherosclerosis. RESULTS: In fact, the angiograms for those patients whose lipid-blood pressure plots were brought below the threshold line exhibited stabilization/regression of coronary atherosclerosis in 75% of cases. It is suggested that the goal of dyslipidaemic therapy should be to bring patient lipid-blood pressure plots below the threshold line so as to stabilize/reverse extant coronary atherosclerosis, apparent or inapparent, in the majority of dyslipidaemic patients.

Coronary Angiography↗
PubMed2000

Clinical features, anthropometric characteristics, and racial influences on the 'white-coat effect' in a single-centre cohort of 1553 consecutive subjects undergoing routine ambulatory blood pressure monitoring.

BACKGROUND: Patients with high office blood pressures but relatively normal readings during daytime ambulatory monitoring have been the subject of much investigation and debate. This clinical finding in part depends on an alerting reaction to the circumstances of the clinical measurement, often described as the 'white-coat effect' (WCE). Little is known of the characteristics of patients that are associated with the white coat effect in a large population of routinely referred patients. OBJECTIVE: To relate the size of the WCE (defined as the difference between office and ambulatory daytime readings) to clinical features that may influence this phenomenon. METHODS: We categorized 1553 consecutive subjects (51.3% men, aged 17-88 years), who had been referred to a single centre for the assessment of suspected hypertension prospectively into three groups: those aged <40, 40-59, and >/=60 years. RESULTS: WCE on systolic blood pressure (SBP) increased significantly with advancing age and was correlated positively to body mass index (BMI), age and treatment. We found significant correlations to sex (higher in women) and race. WCE on diastolic blood pressure (DBP) decreased slightly with advancing age and was correlated positively to BMI and significantly to race and sex. We found no correlation to age or treatment. Caucasians had a greater WCE than did non-Caucasians (P<0. 001 for SBP and DBP) and hypertensives had greater WCE than did normotensives (P<0.0001 for SBP and DBP). Multiple linear regression analysis showed that age and BMI are the most important factors influencing WCE on SBP and DBP. CONCLUSIONS: Factors such as race, age and BMI may exert important influences on the size of WCE possibly via effects on sympathetic nervous system activity.

Adult↗
PubMed1999

Local L-arginine delivery after balloon angioplasty reduces monocyte binding and induces apoptosis.

BACKGROUND: Local administration of L-arginine after balloon angioplasty has been shown to enhance NO generation and inhibit lesion formation. In this study, we assessed the mechanisms by which local delivery of L-arginine inhibits lesion formation. METHODS AND RESULTS: New Zealand White rabbits (n=56) were fed a 1% cholesterol diet. After 1 week, both iliac arteries were balloon-denuded, and a local drug delivery catheter was introduced into both iliac arteries to deliver either L-arginine (800 mg/5 mL with and without 100 microCi L-[2,3-(3)H]-arginine) or saline. Monocyte-endothelial interaction was assessed by functional binding assay; NO activity was measured by chemiluminescence. Intramural administration of radioactively labeled L-arginine led to significantly higher counts in comparison to the contralateral segment for up to 1 week after delivery (676+/-223 versus 453+/-93 cpm/mg; P<0.02); this was associated with significantly higher NO levels in the L-arginine-treated segments (394.4+/-141.6 versus 86.3+/-34.3 nmol/mg; P<0.01). Even after 2 to 3 weeks, monocyte binding was significantly decreased by treatment with L-arginine as compared with saline infusion (P<0.01). After 4 weeks, there was a 9-fold greater number of apoptotic cells in the vessel wall of L-arginine as compared with the saline-treated segments (P<0.05). CONCLUSIONS: Intramural delivery of L-arginine immediately after angioplasty causes a sustained increase in tissue L-arginine levels associated with enhancement of local NO synthesis. The local increase in NO synthesis is associated with an attenuation of monocyte binding and increased apoptosis of resident macrophages. This treatment strategy could be valuable for the prevention and management of restenosis.

Angioplasty, Balloon↗
PubMed1999

A pressure-mediated nonviral method for efficient arterial gene and oligonucleotide transfer.

In this study, we report a method of controlled pressure-mediated delivery of "naked" DNA that achieves efficient and safe arterial gene and oligonucleotide transfer. We demonstrated a pressure-dependent uptake of fluorescein-labeled (FITC) oligonucleotide (ODN) in rabbit carotid arteries with preexisting neointimal hyperplasia, using nondistending intravascular delivery pressures ranging from 0 to 760 mm Hg. At an infusion pressure of 50 mm Hg, 10.5+/-5% of neointimal cell nuclei were positive for nuclear uptake of FITC-ODN 4 days after transfection. With an infusion pressure of 760 mm Hg, the transfection efficiency increased to 84.2+/-5.3% of neointimal cells, and to 64.5+/-11.6 and 92.4+/-5.5% of medial and adventitial cells, respectively. Similar patterns of FITC-ODN uptake were seen in atherosclerotic injured arteries. We also investigated the pressure-mediated delivery of plasmid DNA. Transfection of a luciferase expression plasmid, using an infusion pressure of 760 mm Hg, yielded luciferase expression of 816.6+/-108.6 fg/mg protein in normal rabbit carotid arteries, as compared with 38.9+/-23.7 fg/mg protein at 100 mm Hg. Luciferase expression was significantly higher in pressure-transfected injured atherosclerotic arteries (5467.3+/-1047.6 fg/mg protein at 760 mm Hg). Transfection of beta-galactosidase indicated that significant transgene expression occurred in the neointima and media. These data indicate that this pressure-mediated transfection method yields efficient oligonucleotide delivery and enhances transduction with plasmid DNA in normal as well as injured nonatherosclerotic or atherosclerotic arteries.

Animals↗
PubMed1999

Three year mortality in heart failure patients with very low left ventricular ejection fractions.

BACKGROUND: Left ventricular ejection fraction is a predictor of the outcome in patients with chronic heart failure. Some treatments cause a small increase in ejection fraction and may, thereby, improve prognosis. METHOD: We studied 99 patients with heart failure and very low left ventricular ejection fractions (all < or =20%). Seventy-four patients had ejection fractions of 11-20% and 25 had < or =10%. Patient follow up was censored at three years. RESULTS: Mortality was 74% at three years. Left ventricular ejection fraction was not a predictor of mortality (P = 0.36). In contrast, peak VO2 at the beginning of the study was a strong predictor of outcome (P = 0.002). CONCLUSION: Three year survival is low when ejection fraction is very low. However, once the ejection fraction is < or =20% ejection fraction is no longer a predictor of mortality. These results suggest that it is unlikely that small increases in ejection fraction will be associated with a survival benefit in this group, and treatments aimed at increasing peak VO2 may be more appropriate.

Follow-Up Studies↗
PubMed1999

Endotoxin and immune activation in chronic heart failure: a prospective cohort study.

BACKGROUND: Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure. METHODS: We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months. FINDINGS: Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45). INTERPRETATION: Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.

Acute-Phase Proteins↗
PubMed1999

Exercise intolerance in patients with chronic heart failure and increased expression of inducible nitric oxide synthase in the skeletal muscle.

OBJECTIVES: This study was designed to analyze the effect of iNOS on mitochondrial creatine kinase (mi-CK) expression and exercise capacity in chronic heart failure (CHF). BACKGROUND: The molecular mechanisms underlying exercise intolerance in CHF are still unclear. Expression of inducible nitric oxide synthase (iNOS) and reduced phosphocreatine resynthesis have been described in skeletal muscle of patients with CHF. However, it is unknown whether these phenomena are causally related to each other and to exercise tolerance. METHODS: Thirty-eight patients with CHF and 8 healthy controls (C) underwent bicycle ergospirometry and biopsy of the vastus lateralis muscle. Expression of iNOS was quantified by immunohistochemistry and reverse-transcriptase polymerase chain reaction, mi-CK by Western-blot. Intracellular presence of NO was confirmed by immunohistochemical quantification of nitrotyrosine (NT). To corroborate clinical findings, L6 rat skeletal myoblasts were incubated with sodium nitroprusside (SNP). RESULTS: Expression of iNOS was significantly increased in CHF (4.0+/-2.8 vs. 0.8+/-0.7% iNOS positive tissue area, p < 0.001 vs. C) and inversely correlated to maximal oxygen uptake (r=-0.65, p < 0.001). Intracellular NO-accumulation was confirmed by increased NT levels (13.5+/-8.5 vs. 2.0+/-1.7% NT-positive tissue area, p < 0.001 vs. C). Mi-CK was decreased in CHF (0.84+/-0.36 vs. 1.57+/-0.60, p < 0.001 vs. C). The inverse correlation seen between iNOS and mi-CK expression in patients (r=-0.68, p < 0.001) was reproduced in incubation experiments with SNP. CONCLUSIONS: Increased expression of iNOS in skeletal muscle of patients with CHF was inversely correlated with mi-CK expression and exercise capacity. Cell experiments confirmed a causal relationship via NO. These findings extend our knowledge of the pathophysiology of exercise intolerance in CHF.

Aged↗