Release pattern of cardiac biomarkers in left ventricular apical ballooning.
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Aged↗
Biomedical subjects
Albrecht Elsässer
Publications and source records attributed to Albrecht Elsässer.
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↗
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↗
Multiple episodes of a transient global left ventricular dysfunction reminiscent to apical ballooning.
A new cardiac syndrome with transient left ventricular dysfunction has been recently reported and is referred to as Tako-Tsubo cardiomyopathy, which is characterized by a transient akinesia of the apex and compensatory basal hyperkinesis. Today, the etiology remains unknown. We report for the first time of a patient with multiple episodes of a transient global left ventricular dysfunction which is reminiscent to apical ballooning. These episodes were always preceded by severe emotional stress proposing a potential common pathomechanism.
Cardiomyopathies↗
Temporary third-degree atrioventricular block in a case of apical ballooning syndrome.
Apical ballooning is characterized by severe but reversible contractile dysfunction. The causative factor and the pathomechanism remain unknown. Several arrhythmias are reported to occur in apical-ballooning. We present a unique case of a 58-year-old man presenting with apical ballooning complicated by a prolonged third-degree atrioventricular block requiring the implantation of a pacemaker.
Cardiac Pacing, Artificial↗
Bone marrow-derived cells contribute to infarct remodelling.
OBJECTIVE: The paradigm that cardiac myocytes are non-proliferating and terminally differentiated cells has recently been challenged by several studies reporting the ability of bone marrow-derived cells (BMC) to transdifferentiate into cardiomyocytes. However, these results are controversial and could not be reproduced by others. Therefore, we studied the contribution and potential transdifferentiation of BMC into different cell types during the remodelling process in mouse hearts with experimental myocardial infarction. METHODS: Mice (C57BL/6J) were sublethally irradiated, and BM from enhanced green fluorescent protein (eGFP)-transgenic mice was transplanted. Coronary artery ligation was performed 3 months later. The hearts were studied 7 days (n=13) and 21 days (n=12) after infarction. Immunohistochemical staining was performed using antibodies against titin, connexin 43, vimentin, SMemb alpha-smooth muscle actin, CD45, CD34, F4/80, BS-1, CD31, and eGFP. Sections were analyzed using fluorescence and confocal laser microscopy. RESULTS: Success of BM transplantation was confirmed by FACS analysis. Occlusion of the coronary artery resulted in infarct sizes of 41+/-6% of the left ventricle. CD45+/eGFP+ inflammatory cells were found frequently after 7 days and to a lesser degree after 21 days. In 25 examined hearts, only 3 eGFP-positive cardiomyocytes were found. However, numerous BMC-derived fibroblasts and myofibroblasts were found in the infarct area. BMC contributed to scar tissue neoangiogenesis but not to angiogenesis in the periinfarct and remote zones. CONCLUSION: Transdifferentiation of BMC into viable cardiomyocytes is a negligible event in normal repair processes after myocardial damage. BMC-derived fibroblasts and myofibroblasts as well as neoangiogenesis significantly contribute to post-infarction scar formation and might be important in scar tissue remodelling.
Animals↗
[Striking a new path in medical education. CAMPUS, an interactive, case-based training system].
BACKGROUND AND PURPOSE: Computer-assisted teaching and learning tools offer new opportunities for improving education and training of medical professionals. CAMPUS represents a software for computer-based, problem-oriented learning. It is a case-based training system which provides the patient's history within a highly realistic, multimedia format. Thus, the interactive design is expected to challenge, test and improve the medical knowledge and the diagnostic skills of the students. The objective of the present study was to introduce CAMPUS as a computer-based learning tool and to present preliminary results with regard to acceptance and user-friendliness. METHODS: CAMPUS was evaluated by 52 students regarding quality and experienced learning success. A tutorial was conducted within separate, small-numbered groups of students, each working on one learning case. The virtual case started with a summary of the patient's leading symptoms. The students independently took the patient history and carried out the physical examination. Then, they were asked to suggest differential diagnoses, refer the patient to appropriate diagnostic examinations and were encouraged to choose adequate therapeutic strategies. Subsequently, the quality of CAMPUS and the subjective learning success were evaluated with a standardized questionnaire. RESULTS: Nearly all students described the user interface as visually attractive (51/52) and clearly structured (52/52). In particular, the students found the use of videos to be advantageous. A marked learning success was described by most students (46/52) and all students considered learning with CAMPUS to be effective. CONCLUSION: CAMPUS offers an innovative training program to improve medical education and to enhance conventional teaching methods efficiently.
Attitude of Health Personnel↗
Contractile effects of angiotensin and endothelin in failing and non-failing human hearts.
BACKGROUND: Angiotensin II (Ang II) and endothelin-1 (ET-1) share their effects on growth of myocardial cells but have been shown to elicit different effects on myocardial function. However, these effects vary markedly among species, cardiac regions (atrium or ventricle) and failing or non-failing myocardium. We therefore investigated the effects of both peptides on contractile function of isolated human myocytes from failing and non-failing hearts. METHODS AND RESULTS: Cardiomyocytes were enzymatically isolated and electrically stimulated (15 V, 0.2 Hz). Ang II elicited a positive inotropic effect (PIE) mediated by activation of protein kinase C (PKC) in atrial but no effect in ventricular myocytes. ET-1 (10(-8) M) increased cell-shortening by 146+/-9.3% (p<0.05) in atrial myocytes, by 99.1+/-16.5% (p<0.05) in non-failing ventricular but only by 40.5+/-6.4% (p<0.05) in failing ventricular myocytes. The PIE of ET-1 in failing myocytes was more pronounced at low extracellular pH (+112.6+/-27% at pH 7.0 vs. +40.5+/-6.4% at pH 7.4, p<0.05). Amiloride, a sodium-hydrogen-exchange inhibitor, inhibited two thirds of the PIE of ET-1 in failing myocytes. The PKC-inhibitor decreased the PIE by 50% from 113% to 64% in ventricular myocytes under acidotic conditions. CONCLUSION: Ang II and ET-1 elicited PIE in atrial myocytes, whereas in ventricular myocytes Ang II did not induce PIE in contrast to ET-1. The PIE of ET-1 was markedly attenuated in failing myocytes. Under acidotic conditions, the PIE of ET-1 was more pronounced in failing myocytes, indicating that ET-1 may activate signaling processes in failing myocytes, which are not activated in normal myocytes.
Angiotensin I↗
Images in cardiovascular medicine. Natural tissue engineering inside a ventricular septum defect occluder.
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Aged↗
How to revascularize patients with diabetes mellitus: bypass or stents and drugs?
The diabetic patient is at high risk for coronary artery disease. Incidence as well as severity of the disease is highly increased in comparison to non-diabetic patients. The revascularization of the diabetic patient is a great challenge, since the longterm results are disappointing when compared to non-diabetic patients. The success of coronary artery bypass grafting is limited by increased perioperative mortality and a faster occlusion of especially venous bypass grafts. In percutaneous interventions the excessive high restenosis rates worsen longterm results. Several clinical trials investigated the outcome of the two revascularization strategies and could demonstrate at least a tendency towards better results when the operative approach was chosen. Particularly, the BARI trial showed reduced mortality for surgery when compared to percutaneous coronary interventions. However, in this trial, in 87% of patients undergoing bypass surgery all stenoses were successfully treated, whereas in patients undergoing percutaneous coronary intervention only 76% of all stenoses were primarily successfully treated. In addition, no stents were used in this trial.Furthermore, the enrollment of the previous trials dates one decade ago. These trials do therefore not necessarily represent the current standard therapy, especially for percutaneous coronary interventions. The restenosis rate could be decreased in recent years by means of drug-eluting stents and an aggressive antiplatelet therapy from more than 50% to less than 10% leading to considerably improved long-term results. Therefore, percutaneous coronary interventions have developed to be a reasonable alternative to bypass surgery. Different clinical trials are currently underway (BARI 2D, CarDIA, FREEDOM) comparing the outcome of the two approaches.
Angioplasty, Balloon, Coronary↗
Brief antecedent anoxia preserves mitochondrial function after sustained undersupply: a subcellular correlate to ischemic preconditioning?
BACKGROUND: There is increasing evidence that mitochondria - owning a high degree of autonomy within the cell - might represent the target organelles of the myocardial protection afforded by ischemic preconditioning. It was the aim of the study to investigate a possible subcellular correlate to ischemic preconditioning at the mitochondrial level. In addition, we tested whether this protection depends on mitochondrial ATP-dependent potassium channels (K (ATP)) and an might involve an attenuation of mitochondrial ATP hydrolysis during sustained anoxia. METHODS AND RESULTS: Sustained anoxia (A, 14 min) and reoxygenation (R) completely inhibited state 3 and state 4 respiration of isolated ventricular mitochondria from Wistar rats. An antecedent brief anoxic incubation (4 min) followed by reoxygenation (2 min) prevented this loss of mitochondrial function. The protection afforded by anoxic preconditioning could be mimicked by the K (ATP) opener diazoxide (30 micromol/l) and was completely inhibited by the K (ATP) blocker 5-hydroxydecanoic acid (300 micromol/l). Structural mitochondrial integrity, as estimated from externalization of the mitochondrial enzymes creatine kinase and glutamateoxalacetate transaminase, remained unchanged between the groups, as did mitochondrial ATP loss during anoxia. CONCLUSION: For the first time, we provide direct evidence for a subcellular preconditioning-like functional mitochondrial adaptation to sustained anoxia. This effect apparently depends on opening of K(ATP) but is independent of ATP preservation.
Adaptation, Physiological↗
[Tako-Tsubo cardiomyopathy--a novel cardiac entity?].
In recent years, a new cardiac syndrome with transient left ventricular dysfunction has been widely reported in Japan. This new entity has been referred to as "tako-tsubo cardiomyopathy" or "apical ballooning", named for the particular shape of the end-systolic left ventricle in ventriculography. This syndrome has also been reported to occur in the western population. The clinical characteristics of this phenomenon have been described as follows: (1) acute onset of reversible left ventricular apical wall motion abnormalities (ballooning) with chest pain, (2) electrocardiographic changes (i.e., ST elevation), (3) minimal myocardial enzymatic release, and (4) no significant stenosis on coronary angiography. Severe emotional or physical stress usually precedes this cardiomyopathy. A unifying mechanistic explanation responsible for this acute but rapidly reversible contractile dysfunction is still lacking. Several investigations suggested catecholamine-mediated cardiotoxicity or coronary artery vasospasm, microvascular injury, an impaired fatty acid metabolism, or transient obstruction of the left ventricular outflow. The optimal treatment of patients presenting with this syndrome may depend on the stage of condition, since various pathophysiological mechanisms underlie the final clinical picture.
Biopsy↗
[Acute coronary syndrome with and without ST elevation].
Coronary artery disease accounts for most deaths in western communities. The acute coronary syndrome subsidizes ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina pectoris. They are characterized by an acute onset of chest pain. The high number of acute coronary syndromes of more than 400,000 per year in Germany demonstrates the necessity of guidelines. Such guidelines are available from different cardiac societies. The implementation of the guidelines of the German Cardiac Society and the European Society of Cardiology in the daily clinical practice are demonstrated in this review by means of two case presentations. Special attention has been given to diagnostic measures, risk stratification, and different therapeutic options. For the diagnostic work-up in the acute phase, the ECG and the assessment of cardiac biomarkers play the central role. For patients with ST elevation myocardial infarction, primary interventional diagnostics and therapy are the first choice. For patients presenting with acute coronary syndromes without ST elevation, a risk-adapted therapeutic approach should be chosen. High-risk patients (elevated troponins, clinical, rhythmologic, and hemodynamic instability, ST depression, or diabetes mellitus) should be treated with an early invasive approach within 48-72 h. Low-risk patients can be treated primarily conservatively. For all patients who undergo interventional treatment, administration of an aggressive antiaggregatory therapy, including acetylsalicylic acid, clopidogrel, glycoprotein IIb/IIIa receptor antagonists, and heparin, is indicated in the acute phase. In the chronic phase, an adequate treatment of cardiovascular risk factors is of paramount importance.
Acute Disease↗
Reduced sarcoplasmic reticulum Ca2+ -ATPase activity and dephosphorylated phospholamban contribute to contractile dysfunction in human hibernating myocardium.
Human hibernating myocardium (HHM) is characterized by reversible contractile dysfunction during chronic ischemia. A disturbed calcium-homeostasis is a decisive factor for reduced functional capacity in heart diseases. We therefore investigated calcium-handling proteins in HHM. In 12 patients suffering from multi-vessel coronary artery disease and contractile dysfunction with indication for bypass surgery, HHM was detected preoperatively by thallium scintigraphy, radionuclide ventriculography and dobutamine echocardiography. Transmural biopsies of these regions were taken and analyzed by immunohistochemistry and electron microscopy. Furthermore, SR-calcium ATPase (SERCA2a), phospholamban (PLN), the phosphorylated forms of PLN (PLN-Ser16, PLN-Thr17) as well as sodium-calcium exchanger (NCX) and ryanodine receptor (RyR2) were investigated by RT-PCR and Western-blotting. Additionally, SERCA2a activity was measured by an enzyme-coupled assay. In all patients complete functional recovery could be documented 3 months after revascularization by repeating all preoperative investigations. In HHM maximal SERCA2a activity was significantly reduced (HHM: 424.5 +/- 33.9, control: 609.0 +/- 48.5 nmol ATP mg protein(-1) min(-1), p <or= 0.05), whereas SERCA2a protein levels were unchanged. mRNA levels (HHM: 1.36 +/- 0.08 vs. control: 0.78 +/- 0.04, p <or= 0.05) and protein amount (HHM:1.67 +/- 0.14 vs. control: 1.00 +/- 0.04, p <or= 0.05) of PLN (A1) were increased resulting in an increased PLN:SERCA2a-ratio. PLN-Ser16 (HHM: 0.60 +/- 0.08 vs. control: 1.00 +/- 0.11, p <or= 0.05) and PLN-Thr17 (HHM: 0.63 +/- 0.11 vs. control: 1.00 +/- 0.06, p <or= 0.05) phosphorylation was significantly decreased. RyR2 and NCX showed no significant alteration. In HHM a decreased activity of SERCA2a due to an impaired phosphorylation of PLN contributes to contractile dysfunction. The increase in the relative ratio of PLN/SERCA2a leads to a decreased calcium affinity of SERCA2a.
Aged↗
Primary stenting of the left main coronary artery with anomalous origin from the right sinus of valsalva.
The presence of an aberrant origin of left main coronary artery from the right sinus of valsalva passing between the aorta ascendens and pulmonary trunk is one of the anomalies most frequently associated with malignant clinical events, and surgical treatment is recommended. We report of a 64-year-old patient with a highly increased risk for surgery due to severe chronic obstructive pulmonary disease. This case demonstrates that the use of a drug-eluting stent offers a suitable and valuable alternative.
Abnormalities, Multiple↗
Myocardial preconditioning and remote renal preconditioning--identifying a protective factor using proteomic methods?
It is still unknown whether remote ischemic preconditioning is mediated by a humoral or a neurogenic mechanism from the preconditioning to the preconditioned tissue. The purpose of the following study was to identify a possible humoral trigger of ischemic myocardial preconditioning and remote renal preconditioning. Open chest rats were subjected to a coronary artery occlusion period of 45 min followed by 2 h of reperfusion (Control animals; n = 6). The coronary preconditioned group (IPC, n = 6) was subjected to a preceding preconditioning period of 5 min coronary artery occlusion followed by 5 min of reperfusion, repeated three times. The renal preconditioned group (IPR, n = 6) was subjected to a preceding renal artery occlusion period of 10 min followed by 20 min of reperfusion. Area at risk (AAR) and infarcted area (IA) were determined at the end of each protocol. Blood samples were taken at the end of the preconditioning protocols from parallel experiments for proteomic analysis using two-dimensional gel electrophoresis (2-DE), matrix assisted laser desorption and ionization-time of flight-mass spectrometry (MALDI-TOF-MS), and liquid chromatography-electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS). IA/AAR was 87.8 +/- 10.7% in the control group. IPC and IPR significantly reduced IA/AAR (58.2 +/- 9.3% and 56.9 +/- 9.0%, p < 0.001). Proteomic analyses detected four protein spots which were either up- (n = 3) or down-regulated in the preconditioned groups vs. the control group. The three up-regulated protein spots were identified as albumin fragments, whereas the down-regulated spot was identified as liver regeneration-related protein (LRRG03). Interestingly, albumin modification by brief ischemia has been recently shown and evaluated for the clinical diagnosis of sublethal myocardial ischemia. However, no differentially abundant proteins which possess a known signaling function could be found. Hence, though there is a differential protein expression in blood following IPC and IPR, our data are not in favor of a humoral mediator of remote preconditioning with a molecular weight of more than 8 kDa. Our results rather suggest either a neurogenic pathway or a mediator smaller than 8 kDa.
Albumins↗
Metabolic control analysis of the Warburg-effect in proliferating vascular smooth muscle cells.
The accumulation and proliferation of vascular smooth muscle cells (VSMC) within the vessel wall is an important pathogenic feature in the development of atherosclerosis. Glucose metabolism has been implicated to play an important role in this cellular mechanism. To further elucidate the role of glucose metabolism in atherogenesis, glycolysis and its regulation have been investigated in proliferating VSMC. Platelet derived growth factor (PDGF BB)-induced proliferation of VSMCs significantly stimulated glucose flux through glycolysis. Further evaluating the enzymatic regulation of this pathway, the analysis of flux:metabolite co-responses revealed that anaerobic glycolytic flux is controlled at different sites of gycolysis in proliferating VSMCs, being consistent with the concept of multisite modulation. These findings indicate that regulation of glycolytic flux in proliferating VSMCs differs from traditional concepts of metabolic control of the Embden-Meyerhof pathway.
Becaplermin↗
Transforming growth factor-beta1 downregulates beating frequency and remodeling of cultured rat adult cardiomyocytes.
We have observed increased levels of transforming growth factor-beta1 (TGF-beta1) in human hibernating myocardium (HM). Impaired ventricular function in HM is known to be restored to normal following revascularization implying that myocardial structure in HM is to a certain degree preserved. We have therefore tested whether TGF-beta1 can imitate features of HM by reducing the number and frequency of beating cells (chronotropism) and structural remodeling of cultured adult rat cardiomyocytes (ARC), thus saving substrate, energy, and oxygen. Parameters measured were cell size, protein synthesis, protein degradation, protein content, myofibrillogenesis, and chronotropism. ARC were stimulated for 6 days with sera from patients with coronary heart disease, as this period led to a maximum response of cells. An increase of 90% in cell surface area following such treatment was reduced to a 20% increase of the original size by TGF-beta1. Concomitantly, the rate of protein synthesis dropped from 3.6-fold to 2.4-fold, and myofibrillogenesis was reduced. TGF-beta1 downregulated both the number of contracting cells from 81% to 10% and the frequency from 52 to nine beats per minute. However, TGF-beta1 treatment did not reduce the augmentation of protein content (1.28-fold versus 1.25-fold) indicating that protein degradation was also inhibited. Similar results were obtained with serum from healthy volunteers. The effects of TGF-beta1 were reversible. We conclude that TGF-beta1 constrains protein turnover and beating activity in underperfused myocardium, thus mediating protection by adapting myocytes to shortages in blood supply.
Animals↗