Human Heart (human + heart)

Distribution by Scientific Domains


Selected Abstracts


HUMAN HEART ,-ADRENOCEPTORS: ,1 -ADRENOCEPTOR DIVERSIFICATION THROUGH ,AFFINITY STATES' AND POLYMORPHISM

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007
P Molenaar
SUMMARY 1In atrium and ventricle from failing and non-failing human hearts, activation of ,1 - or ,2 -adrenoceptors causes increases in contractile force, hastening of relaxation, protein kinase A-catalysed phosphorylation of proteins implicated in the hastening of relaxation, phospholamban, troponin I and C-protein, consistent with coupling of both ,1 - and ,2 -adrenoceptors to stimulatory Gsa -protein but not inhibitory Gia -protein. 2Two ,affinity states', namely ,1H and ,1L, of the ,1 -adrenoceptor exist. In human heart, noradrenaline elicits powerful increases in contractile force and hastening of relaxation. These effects are blocked with high affinity by ,-adenoceptor antagonists, including propranolol, (,)-pindolol, (,)-CGP 12177 and carvedilol. Some beta-blockers, typified by (,)-pindolol and (,)-CGP 12177, not only block the receptor, but also activate it, albeit at much higher concentrations (approximately 2 log units) than those required to antagonize the effects of catecholamines. In human heart, both (,)-CGP 12177 and (,)-pindolol increase contractile force and hasten relaxation. However, the involvement of the ,1 -adrenoceptor was not immediately obvious because (,)-pindolol- and (,)-CGP 12177-evoked responses were relatively resistant to blockade by (,)-propranolol. Abrogation of cardiostimulant effects of (,)-CGP 12177 in ,1 -/,2 -adrenoceptor double-knockout mice, but not ,2 -adrenoceptor-knockout mice, revealed an obligatory role of the ,1 -adrenoceptor. On the basis of these results, two ,affinity states' have been designated, the ,1H - and ,1L -adrenoceptor, where the ,1H -adrenoceptor is activated by noradrenaline and blocked with high affinity by beta-blockers and the ,1L -adrenoceptor is activated by drugs such as (,)-CGP 12177 and (,)-pindolol and blocked with low affinity by beta-blockers such as (,)-propranolol. The ,1H - and ,1L -adrenoceptor states are consistent with high- and low-affinity binding sites for (,)-[3H]-CGP 12177 radioligand binding found in cardiac muscle and recombinant ,1 -adrenoceptors. 3There are two common polymorphic locations of the ,1 -adrenoceptor, at amino acids 49 (Ser/Gly) and 389 (Arg/Gly). Their existence has raised several questions, including their role in determining the effectiveness of heart failure treatment with beta-blockers. We have investigated the effect of long-term maximally tolerated carvedilol administration (> 1 year) on left ventricular ejection fraction (LVEF) in patients with non-ischaemic cardiomyopathy (mean left ventricular ejection fraction 23 ± 7%; n = 135 patients). The administration of carvedilol improved LVEF to 37 ± 13% (P < 0.005); however, the improvement was variable, with 32% of patients showing £ 5% improvement. Upon segregation of patients into Arg389Gly-,1 -adrenoceptors, it was found that carvedilol caused a greater increase in left ventricular ejection faction in patients carrying the Arg389 allele with Arg389Arg > Arg389Gly > Gly389Gly. [source]


TNF Receptors Differentially Signal and Are Differentially Expressed and Regulated in the Human Heart

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009
R. S. Al-Lamki
Tumor necrosis factor (TNF) utilizes two receptors, TNFR1 and 2, to initiate target cell responses. We assessed expression of TNF, TNFRs and downstream kinases in cardiac allografts, and compared TNF responses in heart organ cultures from wild-type (WTC57BL/6), TNFR1-knockout (KO), TNFR2KO, TNFR1/2KO mice. In nonrejecting human heart TNFR1 was strongly expressed coincidentally with inactive apoptosis signal-regulating kinase-1 (ASK1) in cardiomyocytes (CM) and vascular endothelial cells (VEC). TNFR2 was expressed only in VEC. Low levels of TNF localized to microvessels. Rejecting cardiac allografts showed increased TNF in microvessels, diminished TNFR1, activation of ASK1, upregulated TNFR2 co-expressed with activated endothelial/epithelial tyrosine kinase (Etk), increased apoptosis and cell cycle entry in CM. Neither TNFR was expressed significantly by cardiac fibroblasts. In WTC57BL/6 myocardium, TNF activated both ASK1 and Etk, and increased both apoptosis and cell cycle entry. TNF-treated TNFR1KO myocardium showed little ASK1 activation and apoptosis but increased Etk activation and cell cycle entry, while TNFR2KO myocardium showed little Etk activation and cell cycle entry but increased ASK1 activation and apoptosis. These observations demonstrate independent regulation and differential functions of TNFRs in myocardium, consistent with TNFR1-mediated cell death and TNFR2-mediated repair. [source]


Donor-Derived Mesenchymal Stem Cells Remain Present and Functional in the Transplanted Human Heart

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
M. J. Hoogduijn
Mesenchymal stem cells (MSC) are characterized by their multilineage differentiation capacity and immunosuppressive properties. They are resident in virtually all tissues and we have recently characterized MSC from the human heart. Clinical heart transplantation offers a model to study the fate of transplanted human MSC. In this study, we isolated and expanded MSC from heart tissue taken before, and 1 week up to 6 years after heart transplantation. MSC from posttransplantation tissue were all of donor origin, demonstrating the longevity of endogenous MSC and suggesting an absence of immigration of recipient MSC into the heart. MSC isolated from transplanted tissue showed an immunophenotype that was characteristic for MSC and maintained cardiomyogenic and osteogenic differentiation capacity. They furthermore preserved their ability to inhibit the proliferative response of donor-stimulated recipient peripheral blood mononuclear cells. In conclusion, functional MSC of donor origin remain present in the heart for several years after transplantation. [source]


Activity of NADPH-Cytochrome P-450 Reductase of the Human Heart, Liver and Lungs in the Presence of (-)-Epigallocatechin Gallate, Quercetin and Resveratrol: An in vitro Study

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2005
Jaroslaw Dudka
The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine. [source]


Comparison of human and porcine aortic valves

CLINICAL ANATOMY, Issue 3 2003
Eugene K.W. Sim
Abstract We compared the anatomy of human and porcine aortic valves. Porcine hearts were collected from the abattoir. Human hearts from patients who had died of non-cardiac causes were examined in the mortuary; only undamaged and anatomically normal hearts were used. Silicon casts were prepared by injecting engineering silicon at 80 mm Hg into the aortic arch. Various features of the aortic valve were measured: circumference, length between the commissural end point and central point of coaptation, surface diameter, and surface area. In total, 12 porcine and 12 human aortic valves were studied. The average circumferences of the human and porcine aortic valves were 8.00 ± 0.2 (SD) cm and 7.90 ± 1.0 cm, respectively. The central point of coaptation in human valves was skewed toward the left coronary cusp, whereas in porcine valves it was skewed toward the non-coronary cusp. In human aortic valves, the non-coronary cusp had the largest surface diameter and surface area with mean measurements of 3.6 ± 0.2 cm and 1.230 ± 0.228 cm2, respectively; the left coronary cusp was smallest for the same variables with measurements of 3.1 ± 0.3 cm and 0.898 ± 0.357 cm2. In porcine valves, the right coronary cusp had the largest surface diameter and surface area with mean measurements of 3.9 ± 0.7 cm and 1.716 ± 0.81 cm2, respectively; the non-coronary cusp was the smallest for the same variables with measurements of 2.9 ± 0.5 cm and 1.023 ± 0.659 cm2. These differences suggest that when using porcine valves as transplant material (e.g., stentless valves), geometric considerations, such as commissural length, may be important. Clin. Anat. 16:193,196, 2003. © 2003 Wiley-Liss, Inc. [source]


Disparity in regional and systemic circulatory capacities: do they affect the regulation of the circulation?

ACTA PHYSIOLOGICA, Issue 4 2010
J. A. L. Calbet
Abstract In this review we integrate ideas about regional and systemic circulatory capacities and the balance between skeletal muscle blood flow and cardiac output during heavy exercise in humans. In the first part of the review we discuss issues related to the pumping capacity of the heart and the vasodilator capacity of skeletal muscle. The issue is that skeletal muscle has a vast capacity to vasodilate during exercise [,300 mL (100 g),1 min,1], but the pumping capacity of the human heart is limited to 20,25 L min,1 in untrained subjects and ,35 L min,1 in elite endurance athletes. This means that when more than 7,10 kg of muscle is active during heavy exercise, perfusion of the contracting muscles must be limited or mean arterial pressure will fall. In the second part of the review we emphasize that there is an interplay between sympathetic vasoconstriction and metabolic vasodilation that limits blood flow to contracting muscles to maintain mean arterial pressure. Vasoconstriction in larger vessels continues while constriction in smaller vessels is blunted permitting total muscle blood flow to be limited but distributed more optimally. This interplay between sympathetic constriction and metabolic dilation during heavy whole-body exercise is likely responsible for the very high levels of oxygen extraction seen in contracting skeletal muscle. It also explains why infusing vasodilators in the contracting muscles does not increase oxygen uptake in the muscle. Finally, when ,80% of cardiac output is directed towards contracting skeletal muscle modest vasoconstriction in the active muscles can evoke marked changes in arterial pressure. [source]


Zebrafish as a model for long QT syndrome: the evidence and the means of manipulating zebrafish gene expression

ACTA PHYSIOLOGICA, Issue 3 2010
I. U. S. Leong
Abstract Congenital long QT syndrome (LQT) is a group of cardiac disorders associated with the dysfunction of cardiac ion channels. It is characterized by prolongation of the QT-interval, episodes of syncope and even sudden death. Individuals may remain asymptomatic for most of their lives while others present with severe symptoms. This heterogeneity in phenotype makes diagnosis difficult with a greater emphasis on more targeted therapy. As a means of understanding the molecular mechanisms underlying LQT syndrome, evaluating the effect of modifier genes on disease severity as well as to test new therapies, the development of model systems remains an important research tool. Mice have predominantly been the animal model of choice for cardiac arrhythmia research, but there have been varying degrees of success in recapitulating the human symptoms; the mouse cardiac action potential (AP) and surface electrocardiograms exhibit major differences from those of the human heart. Against this background, the zebrafish is an emerging vertebrate disease modelling species that offers advantages in analysing LQT syndrome, not least because its cardiac AP much more closely resembles that of the human. This article highlights the use and potential of this species in LQT syndrome modelling, and as a platform for the in vivo assessment of putative disease-causing mutations in LQT genes, and of therapeutic interventions. [source]


Susceptibility of isolated myofibrils to in vitro glutathionylation: Potential relevance to muscle functions,

CYTOSKELETON, Issue 2 2010
Chiara Passarelli
Abstract In this study we investigated the molecular mechanism of glutathionylation on isolated human cardiac myofibrils using several pro-glutathionylating agents. Total glutathionylated proteins appeared significantly enhanced with all the pro-oxidants used. The increase was completely reversed by the addition of a reducing agent, demonstrating that glutathione binding occurs by a disulfide and that the process is reversible. A sensitive target of glutathionylation was ,-actin, showing a different reactivity to the several pro-glutathionylating agents by ELISA. Noteworthy, myosin although highly sensitive to the in vitro glutathionylation does not represent the primary glutathionylation target in isolated myofibrils. Light scattering measurements of the glutathionylated ,-actin showed a slower polymerisation compared to the non-glutathionylated protein and force development was depressed after glutathionylation, when the myofibrils were mounted in a force recording apparatus. Interestingly, confocal laser scanning microscopy of cardiac cryosections indicated, for the first time, the constitutive glutathionylation of ,-cardiac actin in human heart. Due to the critical location of ,-actin in the contractile machinery and to its susceptibility to the oxidative modifications, glutathionylation may represent a mechanism for modulating sarcomere assembly and muscle functionality under patho-physiological conditions in vivo. © 2009 Wiley-Liss, Inc. [source]


Localization of the mosaic transmembrane serine protease corin to heart myocytes

FEBS JOURNAL, Issue 23 2000
John D. Hooper
Corin cDNA encodes an unusual mosaic type II transmembrane serine protease, which possesses, in addition to a trypsin-like serine protease domain, two frizzled domains, eight low-density lipoprotein (LDL) receptor domains, a scavenger receptor domain, as well as an intracellular cytoplasmic domain. In in vitro experiments, recombinant human corin has recently been shown to activate pro-atrial natriuretic peptide (ANP), a cardiac hormone essential for the regulation of blood pressure. Here we report the first characterization of corin protein expression in heart tissue. We generated antibodies to two different peptides derived from unique regions of the corin polypeptide, which detected immunoreactive corin protein of approximately 125,135 kDa in lysates from human heart tissues. Immunostaining of sections of human heart showed corin expression was specifically localized to the cross striations of cardiac myocytes, with a pattern of expression consistent with an integral membrane localization. Corin was not detected in sections of skeletal or smooth muscle. Corin has been suggested to be a candidate gene for the rare congenital heart disease, total anomalous pulmonary venous return (TAPVR) as the corin gene colocalizes to the TAPVR locus on human chromosome 4. However examination of corin protein expression in TAPVR heart tissue did not show evidence of abnormal corin expression. The demonstrated corin protein expression by heart myocytes supports its proposed role as the pro-ANP convertase, and thus a potentially critical mediator of major cardiovascular diseases including hypertension and congestive heart failure. [source]


Validation of the murine aortic arch as a model to study human vascular diseases

JOURNAL OF ANATOMY, Issue 5 2010
Christophe Casteleyn
Abstract Although the murine thoracic aorta and its main branches are widely studied to gain more insight into the pathogenesis of human vascular diseases, detailed anatomical data on the murine aorta are sparse. Moreover, comparative studies between mice and men focusing on the topography and geometry of the heart and aorta are lacking. As this hampers the validation of murine vascular models, the branching pattern of the murine thoracic aorta was examined in 30 vascular corrosion casts. On six casts the intrathoracic position of the heart was compared with that of six younger and six older men of whom contrast-enhanced computer tomography images of the thorax were three-dimensionally reconstructed. In addition, the geometry of the human thoracic aorta was compared with that of the mouse by reconstructing micro-computer tomography images of six murine casts. It was found that the right brachiocephalic trunk, left common carotid artery and left subclavian artery branched subsequently from the aortic arch in both mice and men. The geometry of the branches of the murine aortic arch was quite similar to that of men. In both species the initial segment of the aorta, comprising the ascending aorta, aortic arch and cranial/superior part of the descending aorta, was sigmoidally curved on a cranial/superior view. Although some analogy between the intrathoracic position of the murine and human heart was observed, the murine heart manifestly deviated more ventrally. The major conclusion of this study is that, in both mice and men, the ascending and descending aorta do not lie in a single vertical plane (non-planar aortic geometry). This contrasts clearly with most domestic mammals in which a planar aortic pattern is present. As the vascular branching pattern of the aortic arch is also similar in mice and men, the murine model seems valuable to study human vascular diseases. [source]


Foetal and adult cardiomyocyte progenitor cells have different developmental potential

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2010
Patrick Van Vliet
Abstract In the past years, cardiovascular progenitor cells have been isolated from the human heart and characterized. Up to date, no studies have been reported in which the developmental potential of foetal and adult cardiovascular progenitors was tested simultaneously. However, intrinsic differences will likely affect interpretations regarding progenitor cell potential and application for regenerative medicine. Here we report a direct comparison between human foetal and adult heart-derived cardiomyocyte progenitor cells (CMPCs). We show that foetal and adult CMPCs have distinct preferences to differentiate into mesodermal lineages. Under pro-angiogenic conditions, foetal CMPCs form more endothelial but less smooth muscle cells than adult CMPCs. Foetal CMPCs can also develop towards adipocytes, whereas neither foetal nor adult CMPCs show significant osteogenic differentiation. Interestingly, although both cell types differentiate into heart muscle cells, adult CMPCs give rise to electrophysiologically more mature cardiomyocytes than foetal CMPCs. Taken together, foetal CMPCs are suitable for molecular cell biology and developmental studies. The potential of adult CMPCs to form mature cardiomyocytes and smooth muscle cells may be essential for cardiac repair after transplantation into the injured heart. [source]


Opposite effects of uracil and adenine nucleotides on the survival of murine cardiomyocytes

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2008
Alessia Mazzola
Abstract We previously showed that the human heart expresses all known P2X and P2Y receptors activated by extra-cellular adenine or uracil nucleotides. Despite evidence that, both in humans and rodents, plasma levels of ATP and UTP markedly increase during myocardial infarction, the differential effects mediated by the various adenine- and uracil-preferring myocardial P2 receptors are still largely unknown. Here, we studied the effects of adenine and uracil nucleotides on murine HL-1 cardiomyocytes. RT-PCR analysis showed that HL-1 cardiomyocytes express all known P2X receptors (except for P2X2), as well as the P2Y2,4,6,14 subtypes. Exposure of cardiomyocytes to adenine nucleotides (ATP, ADP or BzATP) induced apoptosis and necrosis, as determined by flow-cytometry. Cell death was exacerbated by tumour necrosis factor (TNF)-,, a cytokine implicated in chronic heart failure progression. Conversely, uracil nucleotides (UTP, UDP and UDPglucose) had no effect ,per se', but fully counteracted the deleterious effects induced by adenine nucleotides and TNF-,, even if added to cardiomyocytes after beginning exposure to these cell death-inducing agents. Thus, exposure of cardiomyocytes to elevated concentrations of ATP or ADP in the presence of TNF-, contributes to cell death, an effect which is counteracted by uracil-preferring P2 receptors. Cardiomyocytes do not need to be ,primed' by uracil nucleotides to become insensitive to adenine nucleotides-induced death, suggesting the existence of a possible ,therapeutic' window for uracil nucleotides-mediated protection. Thus, release of UTP during cardiac ischaemia and in chronic heart failure may protect against myocardial damage, setting the basis for developing novel cardioprotective agents that specifically target uracil-preferring P2Y receptors. [source]


Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1)

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2003
Lubing Zhou
Abstract We have quantitatively measured gene expression for the sodium-dependent glucose cotransporters 1 and 2 (SGLT1 and SGLT2) in 23 human tissues using the method of real time PCR. As predicted, our results revealed that the expression of SGLT1 was very high in the small intestine (1.2E,+,6 molecules/,g total RNA) relative to that in the kidney (3E,+,4 molecules/,g total RNA). Surprisingly, we observed that the expression of SGLT1 in human heart was unexpectedly high (3.4E,+,5 molecules/,g total RNA), approximately 10-fold higher than that observed in kidney tissue. DNA sequencing confirmed that the PCR amplified fragment was indeed the human SGLT1 gene. Moreover, in situ hybridization studies using a digoxigenin (DIG)-labeled antisense cRNA probe corresponding to human SGLT1 cDNA confirm that human cardiomyocytes express SGLT1 mRNA. In contrast, the expression of SGLT2 in human tissues appears to be ubiquitous, with levels ranging from 6.7E,+,4 molecules/,g total RNA (in skeletal muscle) to 3.2E,+,6 molecules/,g total RNA (in kidney), levels 10,100-fold higher than the expression of SGLT1 in the same tissues. Our finding that human cardiomyocytes express high levels of SGLT1 RNA suggests that SGLT1 may have a functional role in cardiac glucose transport. Since several SGLT inhibitors are currently in development as potential anti-diabetic agents, it may be important to assess the functional consequences of inhibition of SGLT1 in the heart. J. Cell. Biochem. 90: 339,346, 2003. © 2003 Wiley-Liss, Inc. [source]


Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1)

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2001
Enders Kai On Ng
Abstract We have cloned and characterized another alternatively spliced isoform of the human four-and-a-half LIM domain protein 1 (FHL1), designated FHL1C. FHL1C contains a single zinc finger and two tandem repeats of LIM domains at the N-terminus followed by a putative RBP-J binding region at the C-terminus. FHL1C shares the same N-terminal two-and-a-half LIM domains with FHL1 but different C-terminal protein sequences. Due to the absence of the exon 4 in FHL1C, there is a frame-shift in the 3, coding region. Sequence analysis indicated that FHL1C is the human homolog of murine KyoT2. The Northern blot and RT-PCR results revealed that FHL1 is widely expressed in human tissues, including skeletal muscle and heart at a high level, albeit as a relatively low abundance transcript in brain, placenta, lung, liver, kidney, pancreas, and testis. In contrast, FHL1C is specifically expressed in testis, skeletal muscle, and heart at a relatively low level compared with FHL1. The expression of FHL1C transcripts was also seen in aorta, left atrium, left, and right ventricles of human heart at low level. Immunoblot analysis using affinity-purified anti-FHL1C antipeptide antibodies confirmed a 20 kDa protein of FHL1C in human skeletal muscle and heart. Unlike FHL1B, which is another FHL1 isoform recently reported by our group and localized predominantly in the nucleus [Lee et al., 1999], FHL1C is localized both in the nucleus and cytoplasm of mammalian cell. J. Cell. Biochem. 82: 1,10, 2001. © 2001 Wiley-Liss, Inc. [source]


Improving k - t SENSE by adaptive regularization

MAGNETIC RESONANCE IN MEDICINE, Issue 5 2007
Dan Xu
Abstract The recently proposed method known as k - t sensitivity encoding (SENSE) has emerged as an effective means of improving imaging speed for several dynamic imaging applications. However, k - t SENSE uses temporally averaged data as a regularization term for image reconstruction. This may not only compromise temporal resolution, it may also make some of the temporal frequency components irrecoverable. To address that issue, we present a new method called spatiotemporal domain-based unaliasing employing sensitivity encoding and adaptive regularization (SPEAR). Specifically, SPEAR provides an improvement over k - t SENSE by generating adaptive regularization images. It also uses a variable-density (VD), sequentially interleaved k - t space sampling pattern with reference frames for data acquisition. Simulations based on experimental data were performed to compare SPEAR, k - t SENSE, and several other related methods, and the results showed that SPEAR can provide higher temporal resolution with significantly reduced image artifacts. Ungated 3D cardiac imaging experiments were also carried out to test the effectiveness of SPEAR, and real-time 3D short-axis images of the human heart were produced at 5.5 frames/s temporal resolution and 2.4 × 1.2 × 8 mm3 spatial resolution with eight slices. Magn Reson Med 57:918,930, 2007. © 2007 Wiley-Liss, Inc. [source]


Age and gender dependence of human cardiac phosphorus metabolites determined by SLOOP 31P MR spectroscopy

MAGNETIC RESONANCE IN MEDICINE, Issue 4 2006
Herbert Köstler
Abstract The aim of this study was to apply 31P magnetic resonance spectroscopy (MRS) using spatial localization with optimal point spread function (SLOOP) to investigate possible age and gender dependencies of the energy metabolite concentrations in the human heart. Thirty healthy volunteers (18 males and 12 females, 21,67 years old, mean = 40.7 years) were examined with the use of 31P-MRS on a 1.5 T scanner. Intra- and interobserver variability measures (determined in eight of the volunteers) were both 3.8% for phosphocreatine (PCr), and 4.7% and 8.3%, respectively, for adenosine triphosphate (ATP). High-energy phosphate (HEP) concentrations in mmol/kg wet weight were 9.7 ± 2.4 (age < 40 years, N = 16) and 7.7 ± 2.5 (age , 40 years, N = 14) for PCr, and 5.1 ± 1.0 (age < 40 years) and 4.1 ± 0.8 (age , 40 years) for ATP, respectively. Separated by gender, PCr concentrations of 9.2 ± 2.4 (men, N = 18) and 8.0 ± 2.8 (women, N = 12) and ATP concentrations of 4.9 ± 1.0 (men) and 4.2 ± 0.9 (women) were measured. A significant decrease of PCr and ATP was found for volunteers older than 40 years (P < 0.05), but the differences in metabolic concentrations between both sexes were not significant. In conclusion, age has a minor but still significant impact on cardiac energy metabolism, and no significant gender differences were detected. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source]


Rapid cine MRI of the human heart using reconstruction by estimation of lines and inhibition of fold-in

MAGNETIC RESONANCE IN MEDICINE, Issue 5 2002
Wolfgang G. Rehwald
Abstract A fast imaging method is described that yields an approximately six-fold acquisition time reduction relative to conventional techniques. The method involves: 1) acquisition of every sixth k -space line; 2) shifting of acquired k -space lines between odd and even frames; and 3) a single-frame correction image. Reconstruction is achieved by temporal interpolation for k -space lines not acquired combined with subtraction of stationary fold-in artifacts. Seven patients with heart disease and one volunteer were evaluated. SNR was measured in myocardium and the ventricular cavity for both the conventional and new technique. The method is best suited for fast imaging of moving objects confined to a small region within a larger stationary object, such as the heart within the thoracic cavity. It can be implemented in cine and functional imaging sequences and, in principle, in perfusion sequences. Magn Reson Med 47:844,849, 2002. © 2002 Wiley-Liss, Inc. [source]


Accurate phosphorus metabolite images of the human heart by 3D acquisition-weighted CSI

MAGNETIC RESONANCE IN MEDICINE, Issue 5 2001
Rolf Pohmann
Abstract Fourier imaging modalities suffer from significant signal contamination between adjacent voxels, especially when the spatial resolution is comparable to the size of the anatomical structures. This contamination can be positive or negative, depending on the spatial response function and the geometry of the object. Such a situation arises in human cardiac 31P chemical shift imaging (CSI). Acquisition-weighted CSI reduces this contamination substantially, which is demonstrated by comparing conventional CSI to Hanning-weighted 3D 31P-CSI experiments in 13 healthy volunteers at 2 T. The nominal spatial resolution and the total number of scans were identical for both experiments. The improved spatial response function of the acquisition-weighted experiment led to a significantly (P < 0.0001) higher myocardial PCr/ATP ratio (2.05 ± 0.31, mean ± SD, N = 33, corrected for saturation and blood contribution) compared to the conventional CSI experiment (1.60 ± 0.46). This is explained by the absence of negative contamination from skeletal muscle, which also resulted in an increase of the observed SNR (from 5.4 ± 1.4 to 7.2 ± 1.4 for ATP). With acquisition-weighted CSI, metabolic images with a nominal resolution of 16 ml could be obtained in a measurement time of 30 min. After correction for the inhomogeneous B1 field of the surface coil, these images show uniform ATP distribution in the entire myocardium, including the posterior wall. Magn Reson Med 45:817,826, 2001. © 2001 Wiley-Liss, Inc. [source]


Standardized T2* map of normal human heart in vivo to correct T2* segmental artefacts

NMR IN BIOMEDICINE, Issue 6 2007
Vincenzo Positano
Abstract A segmental, multislice, multi-echo T2* MRI approach could be useful in heart iron-overloaded patients to account for heterogeneous iron distribution, demonstrated by histological studies. However, segmental T2* assessment in heart can be affected by the presence of geometrical and susceptibility artefacts, which can act on different segments in different ways. The aim of this study was to assess T2* value distribution in the left ventricle and to develop a correction procedure to compensate for artefactual variations in segmental analysis. MRI was performed in four groups of 22 subjects each: healthy subjects (I), controls (II) (thalassemia intermedia patients without iron overload), thalassemia major patients with mild (III) and heavy (IV) iron overload. Three short-axis views (basal, median, and apical) of the left ventricle were obtained and analyzed using custom-written, previously validated software. The myocardium was automatically segmented into a 16-segment standardized heart model, and the mean T2* value for each segment was calculated. Punctual distribution of T2* over the myocardium was assessed, and T2* inhomogeneity maps for the three slices were obtained. In group I, no significant variation in the mean T2* among slices was found. T2* showed a characteristic circumferential variation in all three slices. The effect of susceptibility differences induced by cardiac veins was evident, together with low-scale variations induced by geometrical artefacts. Using the mean segmental deviations as correction factors, an artefact correction map was developed and used to normalize segmental data. The correction procedure was validated on group II. Group IV showed no significant presence of segmental artefacts, confirming the hypothesis that susceptibility artefacts are additive in nature and become negligible for high levels of iron overload. Group III showed a greater variability with respect to normal subjects. The correction map failed to compensate for these variations if both additive and percentage-based corrections were applied. This may reinforce the hypothesis that true inhomogeneity in iron deposition exists. Copyright © 2007 John Wiley & Sons, Ltd. [source]


After Freud: Phantasy and Imagination in the Philosophy of Religion

PHILOSOPHY COMPASS (ELECTRONIC), Issue 1 2008
Beverley Clack
Philosophers of religion have tended to focus on Freud's dismissal of religion as an illusion, thus characterising his account as primarily hostile. Those who wish to engage with psychoanalytic ideas in order to understand religion in a more positive way have tended to look to later psychoanalysts for more sympathetic sources. This paper suggests that other aspects of Freud's own writings might, surprisingly, provide such tools. In particular, a more subtle understanding of the relationship between illusion and reality emerges in his theory, that itself offers a useful way of understanding the meaning and significance of religion for the human animal. By exploring these sources a view of religion emerges which connects it closely with the processes of imagination and creativity. Under this view, religion is more than just a set of hypotheses to be proved or disproved. In religion, we have access to the most deeply rooted wishes and anxieties of the human heart, and thus its investigation enables a deeper understanding of what it is to be a human being. [source]


Analysis of Cardiac Development in the Turtle Emys orbicularis (Testudines: Emidydae) using 3-D Computer Modeling from Histological Sections

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2010
Laura M.F. Bertens
Abstract In this article we present a 3-D modeling study of cardiac development in the European pond turtle, Emys orbicularis (of the reptilian order Testudines). The study is aimed at elucidating the embryonic development of the horizontal septum in the ventricle and underscoring the importance of 3-D reconstructions in studying morphogenesis. Turtles possess one common ventricle, partly divided into three cava by a vertical and a horizontal septum, of which the embryonic origins have so far not been described. We used serial sectioning and computerized high-resolution 3-D reconstructions of different developmental stages to create a chronological overview of cardiogenesis, in order to study this process. This has yielded a new understanding of the development of the horizontal septum and (directly related) the looping of the heart tube. This looping is found to be markedly different from that in the human heart, with the turtle having two clear bends in the part of the heart tube leaving the primitive ventricle, as opposed to one in humans. It is this particular looping that is reponsible for the formation of the horizontal septum. In addition to our findings on the ventricular septation this study has also yielded new insights into the developmental origins of the pulmonary vein. The 3-D reconstructions were built using our platform TDR-3-D base and enabled us to study the developmental processes in specific parts of the turtle heart separately and in three dimensions, over time. The complete 3-D reconstructions have been made available to the reader via internet using our 3-D model browser application, which allows interactive viewing of the models. The browser application can be found on bio-imaging.liacs.nl/galleries/emysorbicularis/TurtleGallery.html, along with additional images of both models and histological sections and animation sequences of the models. By allowing the reader to view the material in such an interactive way, we hope to make optimal use of the new 3-D reconstruction techniques and to engage the reader in a more direct manner. Anat Rec 239:1101,1114, 2010. © 2010 Wiley-Liss, Inc. [source]


Donor-Derived Mesenchymal Stem Cells Remain Present and Functional in the Transplanted Human Heart

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
M. J. Hoogduijn
Mesenchymal stem cells (MSC) are characterized by their multilineage differentiation capacity and immunosuppressive properties. They are resident in virtually all tissues and we have recently characterized MSC from the human heart. Clinical heart transplantation offers a model to study the fate of transplanted human MSC. In this study, we isolated and expanded MSC from heart tissue taken before, and 1 week up to 6 years after heart transplantation. MSC from posttransplantation tissue were all of donor origin, demonstrating the longevity of endogenous MSC and suggesting an absence of immigration of recipient MSC into the heart. MSC isolated from transplanted tissue showed an immunophenotype that was characteristic for MSC and maintained cardiomyogenic and osteogenic differentiation capacity. They furthermore preserved their ability to inhibit the proliferative response of donor-stimulated recipient peripheral blood mononuclear cells. In conclusion, functional MSC of donor origin remain present in the heart for several years after transplantation. [source]


Activity of NADPH-Cytochrome P-450 Reductase of the Human Heart, Liver and Lungs in the Presence of (-)-Epigallocatechin Gallate, Quercetin and Resveratrol: An in vitro Study

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2005
Jaroslaw Dudka
The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine. [source]


HUMAN HEART ,-ADRENOCEPTORS: ,1 -ADRENOCEPTOR DIVERSIFICATION THROUGH ,AFFINITY STATES' AND POLYMORPHISM

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007
P Molenaar
SUMMARY 1In atrium and ventricle from failing and non-failing human hearts, activation of ,1 - or ,2 -adrenoceptors causes increases in contractile force, hastening of relaxation, protein kinase A-catalysed phosphorylation of proteins implicated in the hastening of relaxation, phospholamban, troponin I and C-protein, consistent with coupling of both ,1 - and ,2 -adrenoceptors to stimulatory Gsa -protein but not inhibitory Gia -protein. 2Two ,affinity states', namely ,1H and ,1L, of the ,1 -adrenoceptor exist. In human heart, noradrenaline elicits powerful increases in contractile force and hastening of relaxation. These effects are blocked with high affinity by ,-adenoceptor antagonists, including propranolol, (,)-pindolol, (,)-CGP 12177 and carvedilol. Some beta-blockers, typified by (,)-pindolol and (,)-CGP 12177, not only block the receptor, but also activate it, albeit at much higher concentrations (approximately 2 log units) than those required to antagonize the effects of catecholamines. In human heart, both (,)-CGP 12177 and (,)-pindolol increase contractile force and hasten relaxation. However, the involvement of the ,1 -adrenoceptor was not immediately obvious because (,)-pindolol- and (,)-CGP 12177-evoked responses were relatively resistant to blockade by (,)-propranolol. Abrogation of cardiostimulant effects of (,)-CGP 12177 in ,1 -/,2 -adrenoceptor double-knockout mice, but not ,2 -adrenoceptor-knockout mice, revealed an obligatory role of the ,1 -adrenoceptor. On the basis of these results, two ,affinity states' have been designated, the ,1H - and ,1L -adrenoceptor, where the ,1H -adrenoceptor is activated by noradrenaline and blocked with high affinity by beta-blockers and the ,1L -adrenoceptor is activated by drugs such as (,)-CGP 12177 and (,)-pindolol and blocked with low affinity by beta-blockers such as (,)-propranolol. The ,1H - and ,1L -adrenoceptor states are consistent with high- and low-affinity binding sites for (,)-[3H]-CGP 12177 radioligand binding found in cardiac muscle and recombinant ,1 -adrenoceptors. 3There are two common polymorphic locations of the ,1 -adrenoceptor, at amino acids 49 (Ser/Gly) and 389 (Arg/Gly). Their existence has raised several questions, including their role in determining the effectiveness of heart failure treatment with beta-blockers. We have investigated the effect of long-term maximally tolerated carvedilol administration (> 1 year) on left ventricular ejection fraction (LVEF) in patients with non-ischaemic cardiomyopathy (mean left ventricular ejection fraction 23 ± 7%; n = 135 patients). The administration of carvedilol improved LVEF to 37 ± 13% (P < 0.005); however, the improvement was variable, with 32% of patients showing £ 5% improvement. Upon segregation of patients into Arg389Gly-,1 -adrenoceptors, it was found that carvedilol caused a greater increase in left ventricular ejection faction in patients carrying the Arg389 allele with Arg389Arg > Arg389Gly > Gly389Gly. [source]


The effect of transient balloon occlusion of the mitral valve on left atrial appendage blood flow velocity and spontaneous echo contrast

CLINICAL CARDIOLOGY, Issue 7 2000
Jianan Wang M.D.
Abstract Background: Spontaneous echo contrast (SEC) is a phenomenon that is commonly seen in areas of blood stasis. It is a slowly moving, cloud-like swirling pattern of "smoke" or increased echogenicity recorded on echocardiography. SEC is commonly seen in the left atrium of patients with mitral stenosis or atrial fibrillation. The prescence of SEC has been shown to be a marker of increased thromboembolic risk. Hypothesis: By using transesophageal echocardiography during percutaneous balloon mitral valvotomy (PBMV), the study investigated the relationship between SEC and varying left atrial appendage (LAA) blood flow velocity in the human heart. Methods: Thirty,five patients with rheumatic mitral stenosis underwent percutaneous balloon mitral valvotomy with intraoperative transesophageal echocardiography monitoring. We alternatively measured LAA velocities and observed the left atrium for various grades of SEC (0 = none to 4 = severe) before and after each balloon inflation. Results: Left atrial appendage maximal ejection velocity was reduced from 35 ± 14 to 6 ± 2 mm/s at peak balloon inflation and increased to 40 ± 16 mm/s after balloon deflation. In comparison with the values before balloon inflation and after balloon deflation, LAA velocities were significantly lower (p < 0.001). New or increased SEC grade was observed during 54 of 61 (88%) inflations and unchanged in 7 (12%) inflations at peak balloon inflation. Spontaneous echo contrast became lower in grade after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%), and remained unchanged after 6 deflations (10%). The mean time to achieve maximal SEC grade (2.5 ± 1.2 s) coincided with the mean time to trough LAA velocities (2.3 ±1.1 s) after balloon inflation. Upon deflation, the mean time to lowest SEC grade (2.9 ± 1.8 s) coincided with mean time to achieve maximal LAA velocities (2.7 ± 1.6s). Conclusion: During balloon inflation, the severity of SEC was enhanced with corresponding reduction in LAA flow velocity. Upon balloon deflation, SEC lightens or disappears with increase in LAA flow velocity. [source]


Role of gp130-mediated signalling pathways in the heart and its impact on potential therapeutic aspects

BRITISH JOURNAL OF PHARMACOLOGY, Issue S1 2008
P Fischer
IL-6-type cytokines bind to plasma membrane receptor complexes containing the common signal transducing receptor chain gp130 that is ubiquitously expressed in most tissues including the heart. The two major signalling cascades activated by the gp130 receptor, SHP2/ERK and STAT pathways, have been demonstrated to play important roles in cardiac development, hypertrophy, protection and remodelling in response to physiological and pathophysiological stimuli. Experimental data, both in vivo and in vitro, imply beneficial effects of gp130 signalling on cardiomyocytes in terms of growth and survival. In contrast, it has been reported that elevated serum levels of IL-6 cytokines and gp130 proteins are strong prognostic markers for morbidity and mortality in patients with heart failure or after myocardial infarction. Moreover, it has been shown that the local gp130 receptor system is altered in failing human hearts. In the present review, we summarize the basic principles of gp130 signalling, which requires simultaneous activation of STAT and ERK pathways under the tight control of positive and negative intracellular signalling modulators to provide a balanced biological outcome. Furthermore, we highlight the key role of the gp130 receptor and its major downstream effectors in the heart in terms of development and regeneration and in response to various physiological and pathophysiological stress situations. Finally, we comment on tissue-specific diversity and challenges in targeted pharmacological interference with components of the gp130 receptor system. British Journal of Pharmacology (2008) 153, S414,S427; doi:10.1038/bjp.2008.1; published online 4 February 2008 [source]


HUMAN HEART ,-ADRENOCEPTORS: ,1 -ADRENOCEPTOR DIVERSIFICATION THROUGH ,AFFINITY STATES' AND POLYMORPHISM

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007
P Molenaar
SUMMARY 1In atrium and ventricle from failing and non-failing human hearts, activation of ,1 - or ,2 -adrenoceptors causes increases in contractile force, hastening of relaxation, protein kinase A-catalysed phosphorylation of proteins implicated in the hastening of relaxation, phospholamban, troponin I and C-protein, consistent with coupling of both ,1 - and ,2 -adrenoceptors to stimulatory Gsa -protein but not inhibitory Gia -protein. 2Two ,affinity states', namely ,1H and ,1L, of the ,1 -adrenoceptor exist. In human heart, noradrenaline elicits powerful increases in contractile force and hastening of relaxation. These effects are blocked with high affinity by ,-adenoceptor antagonists, including propranolol, (,)-pindolol, (,)-CGP 12177 and carvedilol. Some beta-blockers, typified by (,)-pindolol and (,)-CGP 12177, not only block the receptor, but also activate it, albeit at much higher concentrations (approximately 2 log units) than those required to antagonize the effects of catecholamines. In human heart, both (,)-CGP 12177 and (,)-pindolol increase contractile force and hasten relaxation. However, the involvement of the ,1 -adrenoceptor was not immediately obvious because (,)-pindolol- and (,)-CGP 12177-evoked responses were relatively resistant to blockade by (,)-propranolol. Abrogation of cardiostimulant effects of (,)-CGP 12177 in ,1 -/,2 -adrenoceptor double-knockout mice, but not ,2 -adrenoceptor-knockout mice, revealed an obligatory role of the ,1 -adrenoceptor. On the basis of these results, two ,affinity states' have been designated, the ,1H - and ,1L -adrenoceptor, where the ,1H -adrenoceptor is activated by noradrenaline and blocked with high affinity by beta-blockers and the ,1L -adrenoceptor is activated by drugs such as (,)-CGP 12177 and (,)-pindolol and blocked with low affinity by beta-blockers such as (,)-propranolol. The ,1H - and ,1L -adrenoceptor states are consistent with high- and low-affinity binding sites for (,)-[3H]-CGP 12177 radioligand binding found in cardiac muscle and recombinant ,1 -adrenoceptors. 3There are two common polymorphic locations of the ,1 -adrenoceptor, at amino acids 49 (Ser/Gly) and 389 (Arg/Gly). Their existence has raised several questions, including their role in determining the effectiveness of heart failure treatment with beta-blockers. We have investigated the effect of long-term maximally tolerated carvedilol administration (> 1 year) on left ventricular ejection fraction (LVEF) in patients with non-ischaemic cardiomyopathy (mean left ventricular ejection fraction 23 ± 7%; n = 135 patients). The administration of carvedilol improved LVEF to 37 ± 13% (P < 0.005); however, the improvement was variable, with 32% of patients showing £ 5% improvement. Upon segregation of patients into Arg389Gly-,1 -adrenoceptors, it was found that carvedilol caused a greater increase in left ventricular ejection faction in patients carrying the Arg389 allele with Arg389Arg > Arg389Gly > Gly389Gly. [source]