Eichhorn S.,German Heart Center Munich |
Mendoza Garcia A.,TU Munich |
Polski M.,German Heart Center Munich |
Spindler J.,German Heart Center Munich |
And 6 more authors.
Australasian Physical and Engineering Sciences in Medicine | Year: 2017
The provision of sufficient chest compression is among the most important factors influencing patient survival during cardiopulmonary resuscitation (CPR). One approach to optimize the quality of chest compressions is to use mechanical-resuscitation devices. The aim of this study was to compare a new device for chest compression (corpuls cpr) with an established device (LUCAS II). We used a mechanical thorax model consisting of a chest with variable stiffness and an integrated heart chamber which generated blood flow dependent on the compression depth and waveform. The method of blood-flow generation could be changed between direct cardiac-compression mode and thoracic-pump mode. Different chest-stiffness settings and compression modes were tested to generate various blood-flow profiles. Additionally, an endurance test at high stiffness was performed to measure overall performance and compression consistency. Both resuscitation machines were able to compress the model thorax with a frequency of 100/min and a depth of 5 cm, independent of the chosen chest stiffness. Both devices passed the endurance test without difficulty. The corpuls cpr device was able to generate about 10–40% more blood flow than the LUCAS II device, depending on the model settings. In most scenarios, the corpuls cpr device also generated a higher blood pressure than the LUCAS II. The peak compression forces during CPR were about 30% higher using the corpuls cpr device than with the LUCAS II. In this study, the corpuls cpr device had improved blood flow and pressure outcomes than the LUCAS II device. Further examination in an animal model is required to prove the findings of this preliminary study. © 2017 Australasian College of Physical Scientists and Engineers in Medicine
Burri M.,TU Munich |
Vogt M.O.,TU Munich |
Horer J.,TU Munich |
Cleuziou J.,TU Munich |
And 5 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2016
OBJECTIVES: Only little data exist on the durability of bioprostheses in the tricuspid position in patients with congenital heart disease (CHD). The aim of the study was to determine the reoperation rate and the valve function after primary implantation. METHODS: Between 1990 and 2013, 51 patients with CHD underwent tricuspid valve (TV) replacement with a bioprosthesis. The median age at operation was 32 years (range: 8-69). The underlying morphology was Ebstein's anomaly in 62% of the patients. Implanted valves included 38 pericardial and 13 porcine valves. All available echocardiographic examinations (n = 714) and clinical data were retrospectively reviewed. Dysfunction was defined as an at least moderate regurgitation or a mean diastolic gradient ≥9 mmHg. Freedom from death, reoperation and prosthetic valve dysfunction was estimated using the Kaplan-Meier method. RESULTS: The 30-day mortality rate was 9%. The estimated survival rate was 86% at one and 80% at ten years. The freedom from reoperation at 1, 5 and 10 years was 100, 86 and 81%, and that from prosthesis dysfunction detected by echocardiography at 1, 5 and 10 years was 89, 66 and 58%, respectively. The main reason for dysfunction was insufficiency (89%). Valve implantation at an age below 16 years was associated with earlier reoperation and dysfunction (the 5-year freedom rate from reoperation/dysfunction was 70%/30% compared with 89%/78% in the rest of the patients, P = 0.016/0.0009). CONCLUSIONS: Serial echocardiography shows a high rate of dysfunction of TV bioprosthesis in patients with CHD, which already occurred a few years after implantation. In patients below 16 years of age, most prostheses are dysfunctional within 5 years. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Broadley S.P.,TU Munich |
Broadley S.P.,University of Lübeck |
Plaumann A.,TU Munich |
Coletti R.,Ludwig Maximilians University of Munich |
And 14 more authors.
Cell Host and Microbe | Year: 2016
Efficient clearance of bacteremia prevents life-threatening disease. Platelet binding to intravascular bacteria, a process involving platelet glycoprotein GPIb and bacterial opsonization with activated complement C3, influences blood clearance and anti-infective immunity. Using intravital microscopy of the bloodstream of mice infected with Listeria monocytogenes, we show that bacterial clearance is not a uniform process but a “dual-track” mechanism consisting of parallel “fast” and “slow” pathways. “Slow clearance” is regulated by time-dependent bacterial opsonization, stochastic platelet binding, and capture of bacteria-platelet-complexes via the complement receptor of the immunoglobulin superfamily, CRIg. The mechanism spares some bacteria from “fast clearance” and rapid destruction in the liver via Kupffer cell scavenger receptors, keeping them available for adaptive immunity induction by splenic CD8α+ dendritic cells. We consistently find “fast” and “slow” clearance patterns for a broad panel of other Gram+ and Gram− bacteria. Thus, dual-track clearance balances rapid restoration of blood sterility with induction of specific antibacterial immunity. © 2016 Elsevier Inc.
Gramlich M.,University of Tübingen |
Gramlich M.,Victor Chang Cardiac Research Institute |
Pane L.S.,TU Munich |
Zhou Q.,University of Tübingen |
And 25 more authors.
EMBO Molecular Medicine | Year: 2015
Frameshift mutations in the TTN gene encoding titin are a major cause for inherited forms of dilated cardiomyopathy (DCM), a heart disease characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure. To date, there are no specific treatment options for DCM patients but heart transplantation. Here, we show the beneficial potential of reframing titin transcripts by antisense oligonucleotide (AON)-mediated exon skipping in human and murine models of DCM carrying a previously identified autosomal-dominant frameshift mutation in titin exon 326. Correction of TTN reading frame in patient-specific cardiomyocytes derived from induced pluripotent stem cells rescued defective myofibril assembly and stability and normalized the sarcomeric protein expression. AON treatment in Ttn knock-in mice improved sarcomere formation and contractile performance in homozygous embryos and prevented the development of the DCM phenotype in heterozygous animals. These results demonstrate that disruption of the titin reading frame due to a truncating DCM mutation can be restored by exon skipping in both patient cardiomyocytes in vitro and mouse heart in vivo, indicating RNA-based strategies as a potential treatment option for DCM. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
Regn M.,TU Munich |
Laggerbauer B.,TU Munich |
Jentzsch C.,TU Munich |
Ramanujam D.,TU Munich |
And 8 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2016
A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. Based on a reported genetic association of PI16 and plasma levels of the chemokine chemerin, we investigated whether PI16 regulates post-translational processing of its precursor pro-chemerin. PI16-deficient mice were engineered and found to generate higher levels of processed chemerin than wildtype mice. Purified recombinant PI16 efficiently inhibited cathepsin K, a chemerin-activating protease, in vitro. Moreover, we show that conditioned medium from PI16-overexpressing cells impaired the activation of pro-chemerin. Together, our data indicate that PI16 suppresses chemerin activation in the myocardium and suggest that this circuit may be part of the cardiac stress response. © 2016 The Author(s)
Lange R.,TU Munich |
Lange R.,German Center for Cardiovascular Research partner site Munich Heart Alliance |
Burri M.,TU Munich |
Eschenbach L.K.,TU Munich |
And 8 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2015
OBJECTIVES: Da Silva's cone repair is a novel technique for surgical reconstruction of the tricuspid valve and the right ventricle (RV) in Ebstein's anomaly. The technique consists of extensive leaflet mobilization, longitudinal plication of the atrialized ventricle and coneshaped reconstruction of the tricuspid valve, allowing for leaflet-to-leaflet coaptation. We evaluated the influence of Da Silva's cone repair on tricuspid competency, right ventricular size and function. METHODS: From February 2010 until July 2013, 20 patients (median age 30.0 years, range 6.6-68.3 years) underwent Da Silva's cone repair. A 4- to 6-mm interatrial communication was left in all patients. Echocardiographic studies and magnetic resonance imaging (MRI) before and after the repair were evaluated. RESULTS: Median follow-up was 11 (0.5-36) months. There were 2 early deaths and no late death. Echocardiography at follow-up revealed mild or absent tricuspid regurgitation in 16 patients. Two patients showed moderate tricuspid insufficiency. MRI studies showed that the mean functional RV end-diastolic volume decreased after surgery (pre 334 [135-656] ml; post 175 [115-404] ml, P < 0.001). The mean RV ejection fraction decreased (pre 47 ± 10%; post 35 ± 13%, P = 0.001), and the mean antegrade net stroke volume of the RV increased (pre 65 ± 28 ml; post 75 ± 30 ml, P = 0.057). CONCLUSIONS: Da Silva's cone repair for Ebstein's anomaly creates excellent valve function in all patients. Consecutively, the size of the RV decreases and the antegrade net stroke volume increases 6 months after the operation. © The Author 2014, 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Lahm H.,TU Munich |
Schon P.,TU Munich |
Doppler S.,TU Munich |
Dressen M.,TU Munich |
And 8 more authors.
Current Genomics | Year: 2015
In many cases congenital heart disease (CHD) is represented by a complex phenotype and an array of several functional and morphological cardiac disorders. These malformations will be briefly summarized in the first part focusing on two severe CHD phenotypes, hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). In most cases of CHD the genetic origin remains largely unknown, though the complexity of the clinical picture strongly argues against a dysregulation which can be attributed to a single candidate gene but rather suggests a multifaceted polygenetic origin with elaborate interactions. Consistent with this idea, genome-wide approaches using whole exome sequencing, comparative sequence analysis of multiplex families to identify de novo mutations and global technologies to identify single nucleotide polymorphisms, copy number variants, dysregulation of the transcriptome and epigenetic variations have been conducted to obtain information about genetic alterations and potential predispositions possibly linked to the occurrence of a CHD phenotype. In the second part of this review we will summarize and discuss the available literature on identified genetic alterations linked to TOF and HLHS. © 2015 Bentham Science Publishers
Stoehr A.,University of Hamburg |
Stoehr A.,German Center for Cardiovascular Research |
Neuber C.,University of Hamburg |
Neuber C.,German Center for Cardiovascular Research |
And 25 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2014
Contraction and relaxation are fundamental aspects of cardiomyocyte functional biology. They reflect the response of the contractile machinery to the systolic increase and diastolic decrease of the cytoplasmic Ca2+ concentration. The analysis of contractile function and Ca2+ transients is therefore important to discriminate between myofilament responsiveness and changes in Ca2+ homeostasis. This article describes an automated technology to perform sequential analysis of contractile force and Ca2+ transients in up to 11 strip-format, fibrin-based rat, mouse, and human fura-2-loaded engineered heart tissues (EHTs) under perfusion and electrical stimulation. Measurements in EHTs under increasing concentrations of extracellular Ca2+ and responses to isoprenaline and carbachol demonstrate that EHTs recapitulate basic principles of heart tissue functional biology. Ca2+ concentration-response curves in rat, mouse, and human EHTs indicated different maximal twitch forces (0.22, 0.05, and 0.08 mN in rat, mouse, and human, respectively; P < 0.001) and different sensitivity to external Ca2+ (EC50: 0.15, 0.39, and 1.05 mM Ca2+ in rat, mouse, and human, respectively; P < 0.001) in the three groups. In contrast, no difference in myofilament Ca2+ sensitivity was detected between skinned rat and human EHTs, suggesting that the difference in sensitivity to external Ca2+ concentration is due to changes in Ca2+ handling proteins. Finally, this study confirms that fura-2 has Ca2+ buffering effects and is thereby changing the force response to extracellular Ca2+. © 2014 the American Physiological Society.
Doppler S.A.,TU Munich |
Deutsch M.-A.,TU Munich |
Lange R.,TU Munich |
Lange R.,German Center for Cardiovascular Research Partner Site Munich Heart Alliance |
And 2 more authors.
International Journal of Molecular Sciences | Year: 2015
Today, the only available curative therapy for end stage congestive heart failure (CHF) is heart transplantation. This therapeutic option is strongly limited by declining numbers of available donor hearts and by restricted long-term performance of the transplanted graft. The disastrous prognosis for CHF with its restricted therapeutic options has led scientists to develop different concepts of alternative regenerative treatment strategies including stem cell transplantation or stimulating cell proliferation of different cardiac cell types in situ. However, first clinical trials with overall inconsistent results were not encouraging, particularly in terms of functional outcome. Among other approaches, very promising ongoing pre-clinical research focuses on direct lineage conversion of scar fibroblasts into functional myocardium, termed “direct reprogramming” or “transdifferentiation.” This review seeks to summarize strategies for direct cardiac reprogramming including the application of different sets of transcription factors, microRNAs, and small molecules for an efficient generation of cardiomyogenic cells for regenerative purposes. © 2015 by the authors; licensee MDPI, Basel, Switzerland.
Manthey H.D.,University of Würzburg |
Cochain C.,TU Munich |
Barnsteiner S.,University of Würzburg |
Karshovska E.,Ludwig Maximilians University of Munich |
And 12 more authors.
Thrombosis and Haemostasis | Year: 2013
The chemokine receptor CCR6 is expressed by various cell subsets implicated in atherogenesis, such as monocytes, Th17 and regulatory T cells. In order to further define the role of CCR6 in atherosclerosis, CCR6-deficient (Ccr6-/-) mice were crossed with low-density lipoprotein receptor-deficient (Ldlr-/-) mice to generate atherosclerosis-prone mice deficient in CCR6. Compared to Ldlr-/- controls, atherosclerotic burden in the aortic sinus and aorta were reduced in Ccr6-/-Ldlr-/- mice fed a high fat diet, associated with a profound depression in lesional macrophage accumulation. Local and systemic distributions of T cells, including frequencies of Th1, Th17 and regulatory T cells were unaltered. In contrast, circulating counts of both Gr-1high and Gr1low monocytes were reduced in Ccr6-/-Ldlr-/- mice. Moreover, CCR6 was revealed to promote monocyte adhesion to inflamed endothelium in vitro and leukocyte adhesion to carotid arteries in vivo. Finally, CCR6 selectively recruited monocytes but not T cells in an acute inflammatory air pouch model. We here show that CCR6 functions on multiple levels and regulates the mobilisation, adhesion and recruitment of monocytes/macrophages to the inflamed vessel, thereby promoting atherosclerosis, but is dispensable for hypercholesterolaemia-associated adaptive immune priming. Targeting CCR6 or its ligand CCL20 may therefore be a promising therapeutic strategy to alleviate atherosclerosis. © Schattauer 2013.