Center for Heart Failure Research
Center for Heart Failure Research
Bogert L.W.J.,University of Amsterdam |
Van Lieshout E.J.,University of Amsterdam |
De Mol B.A.J.M.,TU Eindhoven |
Van Goudoever J.,BMEYE B.V. |
And 3 more authors.
Anaesthesia | Year: 2010
Pulse contour methods determine cardiac output semi-invasively using standard arterial access. This study assessed whether cardiac output can be determined non-invasively by replacing the intra-arterial pressure input with a non-invasive finger arterial pressure input in two methods, Nexfin CO-trek® and Modelflow®, in 25 awake patients after coronary artery bypass surgery. Pulmonary artery thermodilution cardiac output served as a reference. In the supine position, the mean (SD) differences between thermodilution cardiac output and Nexfin CO-trek were 0.22 (0.77) and 0.44 (0.81) l.min-1, for intra-arterial and non-invasive pressures, respectively. For Modelflow, these differences were 0.70 (1.08) and 1.80 (1.59) l.min-1, respectively. Similarly, in the sitting position, differences between thermodilution cardiac output and Nexfin CO-trek were 0.16 (0.78) and 0.34 (0.83), for intra-arterial and non-invasive arterial pressure, respectively. For Modelflow, these differences were 0.58 (1.11) and 1.52 (1.54) l.min-1, respectively. Thus, Nexfin CO-trek readings were not different from thermodilution cardiac output, for both invasive and non-invasive inputs. However, Modelflow readings differed greatly from thermodilution when using non-invasive arterial pressure input. © 2010 The Association of Anaesthetists of Great Britain and Ireland.
Lei P.,Huazhong Agricultural University |
Lei P.,University of Oslo |
Lei P.,Center for Heart Failure Research |
Baysa A.,University of Oslo |
And 11 more authors.
Basic Research in Cardiology | Year: 2013
Liver X receptor (LXR)-α and -β play a major role in lipid and glucose homeostasis. Their expression and function in the heart is not well characterized. Our aim was to describe the expression of LXRs in the murine heart, and to determine effects of cardiac LXR activation on target gene expression, lipid homeostasis and ischemia. Both LXRα and -β were expressed in heart tissues, HL-1 cells and isolated cardiomyocytes as determined by qRT-PCR. Elevated cardiac expression of LXR target genes and LXRβ was observed 24 h after in vivo permanent coronary artery ligation. The synthetic LXR agonist GW3965 induced mRNA expression of the LXR target genes in HL-1 cells and isolated cardiomyocytes. This was associated with a buildup of intracellular triglycerides and expanding lipid droplets as quantified by confocal microscopy. Mice injected with GW3965 had cardiac LXR activation as judged by increased target gene expression and lipid droplet accumulation. GW3965 in vivo and in vitro increased expression of genes inducing triglyceride synthesis, and altered expression of lipid droplet-binding protein genes. GW3965 protected HL-1 cells against hypoxia-reoxygenation induced apoptosis. LXR activation by GW3965 in vivo prior to heart isolation and perfusion with induced global ischemia and reperfusion improved left ventricular contractile function and decreased infarct size. In conclusion, LXRs are expressed in the murine heart in the basal state, and are activated by myocardial infarction. Activation of LXR by the synthetic agonist GW3965 is associated with intracardiac accumulation of lipid droplets and protection against myocardial ischemia-reperfusion injury. © 2012 Springer-Verlag Berlin Heidelberg.
Russell K.,University of Oslo |
Eriksen M.,University of Oslo |
Aaberge L.,University of Oslo |
Wilhelmsen N.,University of Oslo |
And 5 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2013
Left ventricular (LV) dyssynchrony reduces myocardial efficiency because work performed by one segment is wasted by stretching other segments. In the present study, we introduce a novel noninvasive clinical method that quantifies wasted energy as the ratio between work consumed during segmental lengthening (wasted work) divided by work during segmental shortening. The wasted work ratio (WWR) principle was studied in 6 anesthetized dogs with left bundle branch block (LBBB) and in 28 patients with cardiomyopathy, including 12 patients with LBBB and 10 patients with cardiac resynchronization therapy. Twenty healthy individuals served as controls. Myocardial strain was measured by speckle tracking echocardiography, and LV pressure (LVP) was measured by micromanometer and a previously validated noninvasive method. Segmental work was calculated by multiplying strain rate and LVP to get instantaneous power, which was integrated to give work as a function of time. A global WWR was also calculated. In dogs, WWR by estimated LVP and strain showed a strong correlation (r = 0.94) and good agreement with WWR by the LV micromanometer and myocardial segment length by sonomicrometry. In patients, noninvasive WWR showed a strong correlation (r = 0.96) and good agreement with WWR using the LV micromanometer. Global WWR was 0.09 ± 0.03 in healthy control subjects, 0.36 ± 0.16 in patients with LBBB, and 0.21 ± 0.09 in cardiomyopathy patients without LBBB. Cardiac resynchronization therapy reduced global WWR from 0.36 ± 0.16 to 0.17 ± 0.07 (P < 0.001). In conclusion, energy loss due to incoordinated contractions can be quantified noninvasively as the LV WWR. This method may be applied to evaluate the mechanical impact of dyssynchrony. © 2013 the American Physiological Society.
Lauritzen K.H.,Copenhagen University |
Morland C.,University of Oslo |
Puchades M.,University of Oslo |
Holm-Hansen S.,Copenhagen University |
And 8 more authors.
Cerebral cortex (New York, N.Y. : 1991) | Year: 2014
The G-protein-coupled lactate receptor, GPR81 (HCA1), is known to promote lipid storage in adipocytes by downregulating cAMP levels. Here, we show that GPR81 is also present in the mammalian brain, including regions of the cerebral neocortex and hippocampus, where it can be activated by physiological concentrations of lactate and by the specific GPR81 agonist 3,5-dihydroxybenzoate to reduce cAMP. Cerebral GPR81 is concentrated on the synaptic membranes of excitatory synapses, with a postsynaptic predominance. GPR81 is also enriched at the blood-brain-barrier: the GPR81 densities at endothelial cell membranes are about twice the GPR81 density at membranes of perivascular astrocytic processes, but about one-seventh of that on synaptic membranes. There is only a slight signal in perisynaptic processes of astrocytes. In synaptic spines, as well as in adipocytes, GPR81 immunoreactivity is located on subplasmalemmal vesicular organelles, suggesting trafficking of the protein to and from the plasma membrane. The results indicate roles of lactate in brain signaling, including a neuronal glucose and glycogen saving response to the supply of lactate. We propose that lactate, through activation of GPR81 receptors, can act as a volume transmitter that links neuronal activity, cerebral energy metabolism and energy substrate availability. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
PubMed | University of Tromsø, Center for Heart Failure Research and University of Oslo
Type: Journal Article | Journal: Basic research in cardiology | Year: 2016
Acute myocardial infarction (AMI) causes sterile inflammation, which exacerbates tissue injury. Elevated levels of circulating mitochondrial DNA (mtDNA) have been associated with AMI. We hypothesized that mtDNA triggers an innate immune response via TLR9 and NF-B activation, causing cardiomyocyte injury. Murine cardiomyocytes express TLR9 mRNA and protein and were able to internalize fluorescently labeled mouse mtDNA. Incubation of human embryonic kidney cells with serum from AMI patients containing naturally elevated levels of mtDNA induced TLR9-dependent NF-B activity. This effect was mimicked by isolated mtDNA. mtDNA activated NF-B in reporter mice both in vivo and in isolated cardiomyocytes. Moreover, incubation of isolated cardiomyocytes with mtDNA induced cell death after 4 and 24h. Laser confocal microscopy showed that incubation of cardiomyocytes with mtDNA accelerated mitochondrial depolarization induced by reactive oxygen species. In contrast to mtDNA, isolated total DNA did not activate NF-B nor induce cell death. In conclusion, mtDNA can induce TLR9-dependent NF-B activation in reporter cells and activate NF-B in cardiomyocytes. In cardiomyocytes, mtDNA causes mitochondrial dysfunction and death. Endogenous mtDNA in the extracellular space is a danger signal with direct detrimental effects on cardiomyocytes.
News Article | November 28, 2016
The heart is an amazingly adaptable organ, responding to the needs of the organism throughout life, such as through periods of increased demand by pumping harder, faster, and also growing to accommodate longer-term requirements such as that experienced in pregnancy or as a response to intense exercise. Some cardiac diseases, such as prolonged high blood pressure and heart attacks, also cause an increase in the heart's muscle mass but dangerously this results in a reduction in cardiac output and can cause an irregular heart rhythm. This growth is called pathological cardiac hypertrophy and eventually leads to heart failure and death. Cardiovascular diseases account for a third of all deaths in the UK. Now, researchers at the Babraham Institute, UK, University of Leuven, Belgium, University of Oslo, Norway and Karolinska Institute, Sweden, have uncovered the molecular control mechanisms responsible for the different biological changes seen in cardiac hypertrophy induced by pathology compared to exercise. These findings point the way for the design of new treatments for heart disease. Their research, published in the Journal of Clinical Investigation, compared the differences between hypertrophic heart growth in rats as a result of exercise - which is beneficial - and heart growth induced by pathology - in this case, increased load. Specifically, they compared epigenetic marks responsible for locking cells in their final developed state - important for preventing cells from switching to a less differentiated state. Notably for their analysis, the researchers employed a powerful cell sorting technique to allow them to study pure populations of heart muscle cells (cardiomyocytes) rather than a mix of all cell types in the heart - which, due to an alteration in composition during disease, would confound analysis. They found a mechanism explaining how, in the case of pathological cardiac hypertrophy, cardiomyocytes lose their adult cellular state and regress back towards their foetal form, switching on genes that were originally expressed as the heart develops in the embryo and usually permanently switched off after birth. Professor Wolf Reik, Head of the Epigenetics Programme at the Babraham Institute, said: "We found that a very important repressive methylation mark is lost by cells in cardiac hypertrophy. The function of this mark is to lock adult cardiomyocytes in their adult state. The loss of the mark leads to inappropriate gene expression as shown by the re-expression of genes usually only seen late in embryo development." The research also analysed human cardiomyocytes and importantly the same molecular changes were seen, demonstrating that the same epigenetic factors underlie cardiac hypertrophy and disease remodelling in humans. Professor Llewelyn Roderick, former group leader at the Babraham Institute, now Professor in the Department of Cardiovascular Sciences at KU Leuven, commented: "Our research has defined a novel epigenetic-based mechanism which explains the contrasting outcomes of cardiac remodelling caused by exercise and pathology. By identifying the epigenetic determinants and the responsible epigenetic enzymes controlling these different forms of cardiac myocyte hypertrophy, as well as how the epigenetic modifiers are themselves regulated by micoRNAs, we provide a potential strategy for epigenetic therapy for adverse cardiac remodelling. This work highlights the value of collaborative research to allow analysis from physiology to molecule and back again." This work was funded by the BBSRC which provides strategic support to the Babraham Institute, The Royal Society and an Odysseus award from the Research Foundation Flanders FWO to support the aspects of this work undertaken at the Babraham Institute. The collaborative work at the University of Oslo was supported by the KG Jebsen Cardiac Research Center and the Center for Heart Failure Research of the University of Oslo and by the Anders Jahres Fund for the Promotion of Science. At the Karolinska Institute, the work was supported by the Swedish Research Council, the Ragnar Söderberg Foundation, the Jeansson Foundations, and the Åke Wibergs foundation.
Chen Y.,Center for Heart Failure Research |
Chen Y.,Shanghai JiaoTong University |
Pat B.,Center for Heart Failure Research |
Gladden J.D.,Center for Heart Failure Research |
And 6 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2011
Left ventricular (LV) volume overload (VO) causes eccentric remodeling with inflammatory cell infiltration and extracellular matrix (ECM) degradation, for which there is currently no proven therapy. To uncover new pathways that connect inflammation and ECM homeostasis with cellular dysfunction, we determined the cardiac transciptome in subacute, compensated, and decompensated stages based on in vivo hemodynamics and echocardiography in the rat with aortocaval fistula (ACF). LV dilatation at 5 wk was associated with a normal LV end-diastolic dimension-to-posterior wall thickness ratio (LVEDD/PWT; compensated), whereas the early 2-wk (subacute) and late 15-wk (decompensated) ACF groups had significant increases in LVEDD/PWT. Subacute and decompensated stages had a significant upregulation of genes related to inflammation, the ECM, the cell cycle, and apoptosis. These changes were accompanied by neutrophil and macrophage infiltration, nonmyocyte apoptosis, and interstitial collagen loss. At 15 wk, there was a 40-fold increase in the matricellular protein periostin, which inhibits connections between collagen and cells, thereby potentially mediating a side-to-side slippage of cardiomyocytes and LV dilatation. The majority of downregulated genes was composed of mitochondrial enzymes whose suppression progressed from 5 to 15 wk concomitant with LV dilatation and systolic heart failure. The profound decrease in gene expression related to fatty acid, amino acid, and glucose metabolism was associated with the downregulation of peroxisome proliferator associated receptor (PPAR)- α-related and bioenergetic-related genes at 15 wk. In VO, an early phase of inflammation subsides at 5 wk but reappears at 15 wk with marked periostin production along with the suppression of genes related to PPAR- α and energy metabolism. © 2011 by the American Physiological Society.
Botden I.P.G.,Erasmus Medical Center |
Draijer R.,Unilever |
Westerhof B.E.,BMeYe BV |
Westerhof B.E.,Center for Heart Failure Research |
And 6 more authors.
American Journal of Hypertension | Year: 2012
Background Epidemiological data suggest that modest red wine consumption may reduce cardiovascular disease risk. Red wine polyphenols improved human endothelial vascular function and reduced blood pressure (BP) in animal studies, but the results of human intervention studies investigating the effect of red wine polyphenols on BP are inconsistent. The objective was to investigate whether polyphenols extracted from red wine reduce peripheral and central BP in subjects with high-normal BP or grade 1 hypertension.MethodsIn a double-blind, placebo-controlled three-period crossover trial, we assigned 61 subjects (mean age 61.4±8.4 years) with office systolic BP 135 9 mm Hg and diastolic BP 82±8 mm Hg to dairy drinks containing either placebo, 280 mg red wine polyphenols, or 560 mg red wine polyphenols. After each 4-week intervention period, office and 24-h ambulatory BP measurements, and central hemodynamic measurements derived from continuous finger BP recordings were assessed.ResultsPolyphenol treatment did not significantly affect 24-h BP: systolic/diastolic BP was 143 2/84 1 mm Hg after placebo, 143 2/84 1 mm Hg after 280 mg/day of red wine polyphenols, and 142 2/83 1 mm Hg after 560 mg/day. Neither dose of polyphenol treatment changed office or central BP, aortic augmentation index (AIx) or pulse wave reflection index.ConclusionsIntake of red wine polyphenols in two different dosages for 4 weeks did not decrease peripheral or central BP in subjects with a high normal or grade 1 hypertension. Our findings do not support the hypothesis that polyphenols account for the suggested cardiovascular benefits of red wine consumption by lowering BP. © 2012 American Journal of Hypertension, Ltd.
Kubben N.,Center for Heart Failure Research
Nucleus (Austin, Tex.) | Year: 2010
The nuclear envelope and the lamina define the nuclear periphery and are implicated in many nuclear processes including chromatin organization, transcription and DNA replication. Mutations in lamin A proteins, major components of the lamina, interfere with these functions and cause a set of phenotypically diverse diseases referred to as laminopathies. The phenotypic diversity of laminopathies is thought to be the result of alterations in specific protein- and chromatin interactions due to lamin A mutations. Systematic identification of lamin A-protein and -chromatin interactions will be critical to uncover the molecular etiology of laminopathies. Here we summarize and critically discuss recent technology to analyze lamina-protein and-chromatin interactions.
Harms M.P.M.,Center for Heart Failure Research |
Wieling W.,Center for Heart Failure Research |
Colier W.N.J.M.,Radboud University Nijmegen |
Lenders J.W.M.,Radboud University Nijmegen |
And 2 more authors.
Clinical Science | Year: 2010
Leg crossing increases arterial pressure and combats symptomatic orthostatic hypotension in patients with sympathetic failure. This study compared the central and cerebrovascular effects of leg crossing in patients with sympathetic failure and healthy controls. We addressed the relationship between MCA Vmean (middle cerebral artery blood velocity; using transcranial Doppler ultrasound), frontal lobe oxygenation [O2Hb (oxyhaemoglobin)] and MAP (mean arterial pressure), CO (cardiac output) and TPR (total peripheral resistance) in six patients (aged 37-67 years; three women) and age- and gender-matched controls during leg crossing. In the patients, leg crossing increased MAP from 58 (42-79) to 72 (52-89) comparedwith 84 (70-95) to 90 (74-94) mmHg in the controls. MCA Vmean increased from 55 (38-77) to 63 (45-80) and from 56 (46-77) to 64 (46-80) cm/s respectively (P < 0.05), with a larger rise in O2Hb [1.12 (0.52-3.27)] in the patients compared with the controls [0.83 (-0.11 to 2.04) μmol/l]. In the control subjects, CO increased 11% (P < 0.05) with no change in TPR. By contrast, in the patients, CO increased 9% (P < 0.05), but also TPR increased by 13% (P < 0.05). In conclusion, leg crossing improves cerebral perfusion and oxygenation both in patients with sympathetic failure and in healthy subjects. However, in healthy subjects, cerebral perfusion and oxygenation were improved by a rise in CO without significant changes in TPR or MAP, whereas in patients with sympathetic failure, cerebral perfusion and oxygenation were improved through a rise in MAP due to increments in both CO and TPR.