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Biomedical subjects

Rainer Hambrecht

Publications and source records attributed to Rainer Hambrecht.

At least 19 recordsLinked to original sources
PubMed2006

Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial.

AIMS: To investigate the clinical outcome after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Using a double-blind, placebo-controlled multicentre trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone-marrow-derived progenitor cells (BMCs) or placebo medium into the infarct artery 3-7 days after successful infarct reperfusion therapy. At 12 months, the pre-specified cumulative endpoint of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (P=0.009). Likewise, the combined endpoint death, recurrence of myocardial infarction, and rehospitalization for heart failure was significantly (P=0.006) reduced in patients receiving intracoronary BMC administration. Intracoronary administration of BMC remained a significant predictor of a favourable clinical outcome by Cox regression analysis, adjusting for classical predictors of poor outcome after AMI. CONCLUSION: Intracoronary administration of BMCs is associated with a significant reduction of the occurrence of major adverse cardiovascular events after AMI. Large-scale studies are warranted to confirm the effects of BMC administration on mortality and morbidity in patients with AMIs.

Adolescent↗
PubMed2006

Myocardial expression of Murf-1 and MAFbx after induction of chronic heart failure: Effect on myocardial contractility.

OBJECTIVE: In chronic heart failure (CHF) the myocardial expression of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha), which is thought to contribute to myocardial remodeling, was found to be increased. However, it is unknown whether the E3-ubiquitin ligases MAFbx and Murf-1 are involved in this remodeling process and whether their expression is regulated by TNF-alpha. METHODS: Rats underwent ligation of the left coronary artery to induce CHF or were sham-operated. The expression of MAFbx/Murf-1 and troponin I was analyzed by RT-PCR and Western blotting in the non-infarcted area of the left ventricle. In cell culture experiments the potency of TNF-alpha to stimulate Murf-1/MAFbx expression, the intracellular signaling pathway, and the involvement of the E3-ligases for the impairment of contractility were assessed. RESULTS: In CHF the myocardial expression of TNF-alpha was elevated 3.1-fold as compared to control. This was associated with a 4.5-fold and 2.7-fold increase in MAFbx and Murf-1 expression, respectively. A positive correlation between TNF-alpha and the expression of MAFbx or Murf-1 was evident. In neonatal rat cardiomyocytes, TNF-alpha induced the expression of MAFbx through p38MAPK-dependent pathways, whereas the induction of Murf-1 required the activation of the p42/44 MAPK pathway. Exposure of cardiomyocytes to TNF-alpha resulted in troponin I ubiquitinylation, subsequent degradation, and a decline in contractility. This was completely abrogated by siRNAs against Murf-1/MAFbx. CONCLUSION: TNF-alpha, which is increasingly expressed in CHF, induces troponin I degradation through a MAFbx/Murf-1-dependent pathway. This was associated with an impairment of contractility and might be one mechanism involved in the adverse remodeling process in CHF.

Animals↗
PubMed2006

Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.

BACKGROUND: Pilot trials suggest that the intracoronary administration of autologous progenitor cells may improve left ventricular function after acute myocardial infarction. METHODS: In a multicenter trial, we randomly assigned 204 patients with acute myocardial infarction to receive an intracoronary infusion of progenitor cells derived from bone marrow (BMC) or placebo medium into the infarct artery 3 to 7 days after successful reperfusion therapy. RESULTS: At 4 months, the absolute improvement in the global left ventricular ejection fraction (LVEF) was significantly greater in the BMC group than in the placebo group (mean [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline LVEF at or below the median value of 48.9% derived the most benefit (absolute improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year, intracoronary infusion of BMC was associated with a reduction in the prespecified combined clinical end point of death, recurrence of myocardial infarction, and any revascularization procedure (P=0.01). CONCLUSIONS: Intracoronary administration of BMC is associated with improved recovery of left ventricular contractile function in patients with acute myocardial infarction. Large-scale studies are warranted to examine the potential effects of progenitor-cell administration on morbidity and mortality.

Aged↗
PubMed2006

Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress: the EPAS trial.

BACKGROUND: Statins and angiotensin type 1 (AT1) receptor blockers reduce cardiovascular mortality and morbidity. In the Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress (EPAS) trial, impact of independent or combined statin and AT1 receptor blocker therapy on endothelial expression of anti-atherosclerotic and proatherosclerotic genes and endothelial function in arteries of patients with coronary artery disease were tested. METHODS AND RESULTS: Sixty patients with stable coronary artery disease undergoing elective coronary artery bypass grafting (CABG) surgery were randomized 4 weeks before surgery to: (A) control without inhibition of renin-angiotensin system or statin; (B) statin (pravastatin 40 mg/d); (C) AT1 blockade (irbesartan 150 mg/d); or (D) combination of statin and AT1 blocker in same dosages. Primary end point was a priori therapy-dependent regulation of an anti-atherosclerotic endothelial expression quotient Q including mRNA expression (in arbitrary units measured by real-time polymerase chain reaction) of endothelial nitric oxide synthase and C-type natriuretic peptide, divided by expression of oxidized low-density lipoprotein receptor LOX-1 and NAD(P)H oxidase subunit gp91phox in left internal mammary arteries biopsies obtained by CABG surgery; 49 patients completed the study. Statin therapy increased lnQ from 3.2+/-0.4 to 4.4+/-0.4 significantly versus control. AT(1) blockade showed a trend to increase lnQ to 4.2+/-0.5. Combination of statin and AT1 blocker further increased lnQ to 5.1+/-0.6, but a putative interaction of both therapies in lnQ was not significant. Furthermore, preoperative therapy with statin, AT1 blocker and their combination improved endothelial function in internal mammary artery rings. CONCLUSIONS: Statin and AT1 blocker therapy independently and in combination improve an anti-atherosclerotic endothelial expression quotient and endothelial function.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Transapical approach for sutureless stent-fixed aortic valve implantation: experimental results.

OBJECTIVE: Percutaneous aortic valve implantation has been performed in patients with severe aortic stenosis judged as nonsurgical candidates. We evaluated a facilitated transapical antegrade approach for potential use in surgical high-risk patients. METHODS: A pericardial xenograft fixed within a 23-mm stent (Cribier-Edwards aortic prosthesis, Edwards Inc., Irvine, CA, USA) was implanted using a transapical approach in fifteen 35-45 kg pigs. A limited or a full sternotomy was used to transapically introduce a crimped valve through a 24-F sheath. Deployments were performed on the beating heart either with ventricular unloading using femoro-femoral cardiopulmonary bypass (CPB) or rapid ventricular pacing (RVP), all under fluoroscopic and echocardiographic visualization. RESULTS: All valves were successfully deployed at the target site with acceptable visualization of the noncalcified annulus. Valve migration occurred in six procedures (three distal and three retrograde) secondary to inadequate reduction of ventricular output, unfavorable annular anatomy, excessive crimping of the valve, and dislodgement by the delivery balloon. Exact positioning of the valve into the target area was confirmed by autopsy at the end of the procedures. Paravalvular leak was noted in five implants. CONCLUSIONS: The transapical approach provides a safe, accurate, and effective route for facilitated antegrade delivery of a stent-fixed valve. Advanced stent design will lead to better stability of the implant and may minimize the risk of paravalvular leakage in future. Identifying the appropriate population for human feasibility trials remains a challenge.

Animals↗
PubMed2006

Reproducibility of chronic and acute infarct size measurement by delayed enhancement-magnetic resonance imaging.

OBJECTIVES: The aim of this study was to evaluate the reproducibility of acute and chronic infarct size (IS) by delayed enhancement (DE) magnetic resonance imaging (MRI). BACKGROUND: Infarct size measurements can be used as surrogate end point to reduce the sample size in studies comparing different reperfusion strategies in myocardial infarction (MI). Delayed enhancement MRI is a rather new technique, and so far infarct IS reproducibility has not been established appropriately. METHODS: In 21 patients (10 acute MI and 11 chronic MI), IS was assessed repeatedly on consecutive days by DE-MRI. Reproducibility, interobserver, and intraobserver variabilities were assessed and compared by the Bland-Altman method. RESULTS: Acute and chronic IS were 17.1 +/- 19.6% (range 5.1% to 69.8%) of LV mass (%LV) and 16.9 +/- 9.9 %LV (range 2.0% to 36.0%), respectively. Infarct size difference (bias) between scan I and scan II was -0.5 %LV, and limits of agreement were +/-2.4 %LV. Mean bias (-0.7 %LV) and limits of agreement (+/-3.2%) were slightly higher for acute in comparison with chronic MI with -0.4 +/- 1.3 %LV. Intraobserver and interobserver variability was low with a mean bias of 0.3 %LV (limits of agreement +/- 1.7 %LV) and -0.7 %LV (limits of agreement +/- 2.2 %LV), respectively. CONCLUSIONS: Infarct size measurement by DE-MRI is an excellent tool for IS assessment, owing to its excellent repeatability in chronic and acute MI. It has therefore the potential to serve as a surrogate end point to uncover advantages of new reperfusion strategies.

Acute Disease↗
PubMed2006

[Exercise training in the treatment of coronary artery disease and obesity].

Endothelial dysfunction has been identified as a major predictor of future cardiovascular events and precedes the development of coronary artery disease (CAD). Regular physical exercise training--as part of a multifactorial intervention--corrects endothelial dysfunction, improves symptoms in patients with CAD, augments myocardial perfusion, and reduces mortality of these patients. This review discusses potential mechanisms, which might be responsible for the exercise training-mediated reduction of mortality in secondary prevention. The activation of stem cells, which are known to regenerate damaged endothelium and promote the development of new vessels by vasculogenesis, the regression of atherosclerosis, the formation of collaterals, and the partial correction of endothelial dysfunction as a consequence of molecular adaptations will be evaluated in this context. However, the positive effects of exercise training in primary and secondary prevention of cardiovascular diseases are not restricted to the correction of endothelial dysfunction. Regular physical activity, either alone or as part of a multifactorial intervention consisting of diet and exercise training, is known to promote effective weight loss. Especially in patients with metabolic syndrome, weight reduction beneficially effects blood glucose control. It increases the levels of vasculoprotective high-density lipoprotein and augments the physical exercise capacity of these individuals. Additionally, regular physical activity attenuates the diet-induced loss in fat-free body mass by 50%, improves body composition and counteracts the reduction in basal energy expenditure, which is another big advantage compared to diet alone in the treatment of obesity. Moreover, physical exercise training is essential to maintain a body weight that has been achieved by caloric restriction. It is important to look for exercise interventions that can easily be integrated in daily life and are not associated with an increased risk of trauma, even in severely obese individuals. Most importantly, patients should enjoy the proposed kind of physical exercise.

Clinical Trials as Topic↗
PubMed2006

Coronary atherosclerosis and cardiovascular risk in masters male marathon runners. Rationale and design of the "marathon study".

BACKGROUND: Regular physical exercise is recommended to reduce cardiovascular mortality. And yet, atherosclerosis is the main cause of exercise-associated death in persons beyond age 35. The need for risk stratification in marathon runners is under discussion. The predictive value of modern imaging- and non-imaging-based markers of risk that can be used for risk stratification in masters endurance athletes still deserves exploration. METHODS: Male runners > 50 years who have completed at least five marathon races during the preceding 3 years and do not suffer from coronary artery disease, angina nor diabetes mellitus are studied to assess the predictive value of established and modern imaging- based and biochemical cardiovascular risk factors. Laboratory parameters including clinical chemistry, hematology and hormone measurements are determined. Lifestyle-related risk factors, psychosocial and socioeconomic variables are explored using standardized questionnaires. Coronary, carotid, femoral and aortic atherosclerosis is measured using electronbeam computed tomography and ultrasound. In addition, a resting ECG, a bicycle stress test and heart rate variability are performed. Myocardial morphology and function are assessed using echocardiography and magnetic resonance imaging. Participants are invited to compete in a marathon race to quantify the association of coronary atherosclerosis with marathon-related changes of cardiac troponin levels and the extent of marathon-induced inflammation. At the cellular level, the effect on the amount of circulating progenitor cells (EPCs) is determined by FACS analysis. Changes in laboratory parameters and hormone levels are also studied. Annual long-term follow-up including hospital records and death certificates is performed. Data are compared with those from a general unselected cohort from the Heinz Nixdorf Recall Study. CONCLUSION: This study should contribute to cardiovascular risk assessment in the growing number of masters marathon runners with a focus on assessing the predictive value of modern imaging techniques and biochemical markers for comprehensive risk stratification.

Adult↗
PubMed2006

Transapical aortic valve implantation: an animal feasibility study.

BACKGROUND: Percutaneous aortic valve implantation has recently been performed in nonsurgical patients with severe aortic stenosis. Retrograde valve delivery has been problematic because of the size of the delivery system and concomitant peripheral vascular disease. We investigated a minimally invasive approach through the left ventricular apex for antegrade placement of a device-deliverable valve. METHODS: Transapical aortic valve implantation was performed using a 23-mm equine valve mounted on a stainless steel stent in 24 swine (weight range, 35 to 45 kg). A limited or full sternotomy approach was used to access the apex of the heart. The crimped valve was introduced through a sheath in the left ventricular apex. Fluoroscopy and echocardiography were used for guidance. Deployments were performed on the beating heart either with ventricular unloading using femoral extracorporeal circulation or rapid ventricular pacing. RESULTS: All valves were successfully delivered at the selected target site with acceptable visualization of the noncalcified aortic annulus. Valve migration occurred during eight deployments (two distal and six retrograde) secondary to persistent cardiac output, unfavorable annular anatomy, and dislodgement by the delivery catheter. Exact positioning of the nonmigrated valves at the aortic annulus was examined by necropsy of all animals at the end of the procedures. Paravalvular leak was noted in 14 of 18 (77.8%) valves remaining in situ. CONCLUSIONS: The transapical approach was used for the successful antegrade placement of a stented valve, obviating the technical problems associated with a large delivery system transiting the peripheral vascular system. Stent design contributing to paravalvular leak remains problematic.

Animals↗
PubMed2006

Effects of exercise training on mortality in patients with coronary heart disease.

Endothelial dysfunction not only precedes the development of significant coronary artery stenosis, it has also been identified as a general phenomenon predicting future cardiovascular events in patients who are at risk. As regular physical activity as a part of a multifactorial intervention has been shown to affect symptoms beneficially, increase myocardial perfusion and--most importantly--reduce mortality in patients with coronary heart disease or myocardial infarction, this review will elucidate potential mechanisms responsible for the improvement in survival as a result of regular physical activity. The importance of exercise training-mediated regression of coronary stenosis, collateral formation, correction of endothelial dysfunction including the adaptation at the molecular level, as well as vasculogenesis will be discussed as possible underlying key players, and their potential contribution to the training-induced survival benefit in patients with coronary heart disease will be critically evaluated.

Coronary Circulation↗
PubMed2006

Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part II: How to perform cardiopulmonary exercise testing in chronic heart failure.

Basic and practical information related to equipment, methodology, exercise protocols, conduct of the test and quality control issues for cardiopulmonary exercise testing (CPET) will be addressed in this II part of the statement. CPET users have the responsibility for assuring that measurements remain accurate. CPT, especially when it features breath-by-breath gas exchange analysis, requires meticulous attention to calibration procedures to assure accurate and reproducible measurements. Skills and knowledge of personnel for supervision and test interpretation, as well as patient preparation and information are key features for a correct CPET conduction: all these issues will be faced. Finally, after the test, the investigator needs to format the results in a manner that optimises the ability to discriminate essential response features; that is, to establish 'interpretive clusters' of the variables of interest. An example of a cardiopulmonary summary exercise test data report will be provided, defining the most important information that should be incorporated in a final report.

Cardiology↗
PubMed2006

Time-course of endothelial adaptation following acute and regular exercise.

BACKGROUND: Regular exercise training has emerged as a powerful tool to improve endothelium-dependent vasorelaxation. However, little is known about the magnitude of change and the permanence of exercise-induced adaptations in endothelial function. DESIGN: Rats were randomized to either 6 weeks of regular exercise or one bout of exercise. Rats were then sacrificed 0, 6, 12, 24, 48, 96 or 192 h post-exercise, and vascular responsiveness to acetylcholine was determined. METHODS: Endothelium-dependent dilation was assessed by exposure to accumulating doses of acetylcholine in ring segments of the abdominal aorta from female Sprague-Dawley rats that either exercised regularly for 6 weeks or performed a single bout of exercise. RESULTS: A single exercise session improved endothelium-dependent vasodilatation for about 48 h. Six weeks of regular exercise induced a significantly larger improvement that lasted for about 192 h. Sensitivity to acetylcholine was twofold higher in chronically trained animals than in those exposed to a single bout of exercise. The decay after a single bout of exercise was about eightfold faster than that after 6 weeks of training. CONCLUSION: The present data extend our concept of exercise-induced adaptation of endothelium-dependent vasodilatation in two regards: (1) a single bout of exercise improves endothelium-dependent dilation for about 2 days, with peak effect after 12-24 h; (2) regular exercise further improves adaptation and increases the sensitivity to acetylcholine approximately fourfold, which slowly returns to sedentary levels within a week of detraining.

Acetylcholine↗
PubMed2006

Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure.

Cardiopulmonary exercise testing (CPET) provides a global assessment of the integrated response to exercise involving the pulmonary, cardiovascular, haematopoietic, neuropsychological, and skeletal muscle systems. This information cannot be obtained through investigation of the individual organ systems in isolation. The non-invasive, dynamic physiological overview permits the evaluation of both submaximal and peak exercise responses, providing the physician with relevant information for clinical decision making. The use of CPET in management of the chronic heart failure patient is increasing with the understanding that resting pulmonary and cardiac function testing cannot reliably predict exercise performance and functional capacity and that, furthermore, overall health status and prognosis are predicted better by indices of exercise tolerance than by resting measurements. Our aim is to produce a statement which provides recommendations on the interpretation and clinical application of CPET in heart failure, based on contemporary scientific knowledge and technical advances: the focus is on clinical indications, issues of standardization, and interpretative strategies for CPET.

Cardiac Output↗
PubMed2006

Both T-786C and G894T polymorphism of endothelial nitric oxide synthase affect in-vitro endothelium-dependent relaxation of internal mammary artery rings from patients with coronary artery disease.

OBJECTIVES: Polymorphisms of endothelial nitric oxide synthase (eNOS) gene in the promoter (T-786C) and exon 7 (G894T) have been suggested to attenuate endothelial function. As it is unknown whether these polymorphisms, on top of classical risk factors, further deteriorate endothelium-dependent vasomotion, we aimed to elucidate the impact of both polymorphisms on the ex-vivo vasomotor function of left internal mammary artery rings from patients with coronary artery disease (CAD) undergoing coronary bypass surgery (CABG). METHODS: Mammary artery rings from 51 consecutive patients with CAD were obtained during elective CABG. Endothelium-dependent ring relaxation was measured in vitro in an organ chamber using acetylcholine (10 to 3 x 10 mol/l). Polymorphisms were determined by polymerase chain reaction restriction length polymorphism. RESULTS: Thirty-three per cent of patients were positive for the T-786C polymorphism, 25% for the G894T polymorphism, and 18% carried mutated alleles in both loci. Maximal acetylcholine-induced ring relaxation was 46.7+/-3.2% in T-786C, 59.6+/-4.2% in G894T, and 66.7+/-7.4% in T-786C/G894T compared with 94.9+/-2.0% in wild-type subjects (P<0.05 versus T-786C, G894T, T-786C/G894T). Patients positive for an eNOS polymorphism with more than three cardiovascular risk factors displayed a further attenuation of acetylcholine-mediated relaxation (45+/-6 %) compared with having up to three risk factors (59+/-3%, P<0.05). CONCLUSION: In patients with CAD, in-vitro assessed endothelium-dependent relaxation of mammary arteries was significantly impaired in those positive for the T-786C or the G894T eNOS polymorphism. These results suggest that the presence of either one of the eNOS polymorphisms deteriorated endothelium-dependent vasodilatory capacity of large conduit vessels on top of classical risk factors in patients with CAD.

Aged↗
PubMed2005

Comparison of bare-metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery: a 5-year follow-up.

BACKGROUND: Randomized trials comparing stenting with minimally invasive direct coronary artery bypass surgery in patients with isolated proximal left anterior descending lesions have shown a significantly higher reintervention rate for stenting and similar results for mortality and reinfarction at short-term follow-up. Long-term follow-up data are sparse. METHODS AND RESULTS: Patients with isolated proximal left anterior descending stenosis were randomized to either surgery (n=110) or bare-metal stenting (n=110). At 5 years, follow-up data were obtained with respect to the primary end point of death, reinfarction, or repeated target vessel revascularization. Clinical symptoms were assessed by the Canadian Cardiovascular Society (CCS) classification. Follow-up information was completed for 216 patients (98.2%), and mean follow-up was 5.6+/-1.2 years. With respect to mortality (surgery, 12%; stenting, 10%; P=0.54) and reinfarctions (surgery, 7%; stenting, 5%; P=0.46), there were no differences between treatment strategies. The need for repeated target vessel revascularization was significantly higher after stenting (32%) compared with surgery (10%; P<0.001). Clinical symptoms improved significantly in both treatment groups compared with baseline; however, there was a favorable trend for surgery (stenting: CCS, 2.6+/-0.9 to 0.5+/-0.8, P<0.001; surgery: CCS, 2.6+/-0.9 to 0.3+/-0.6, P<0.001; P=0.05, stenting versus surgery). CONCLUSIONS: At the 5-year follow-up, minimally invasive bypass surgery and bare-metal stenting showed similar results for the end points of mortality and reinfarctions. However, the reintervention rate is higher after stenting, and the relief in clinical symptoms is slightly better after surgery.

Aged↗