I point my heart with the tip of my fingers–Biometry for the diagnosis of congenital heart defects

Congenital heart defects are characterized by abnormal positioning of some anatomical structures relative to a normal heart. Classically the classification of the disease or the stage of the disease is based on the measurement of the relative position of these structures by the cardiac morphologist. We propose a method in which the heart volume is acquired by a CT scanner. In this paper we present a tool which allows us to define landmarks interactively in this heart volume. These landmarks are then used to estimate some simple geometrical models of the anatomical structures and so as to describe their relative position and orientation.     

Some properties of isolated mitochondrial ATPase from salmon heart

A soluble Mg-dependent ATPase, similar to the mitochondrial ATPase from beef heart, has been isolated from heart mitochondria of salmon (Salmo salar). The salmon heart ATPase has 5 subunits with molecular weights similar to the beef heart enzyme, but the Stoke's radius of the intact salmon enzyme is larger. The salmon heart ATPase is less temperature labile than the beef heart enzyme. The salmon heart ATPase is strongly inhibited by ADP, and the inhibition is highly temperature dependent. The ITPase activity is also inhibited by IDP (Ki = 180 micron). 2,4-Dinitrophenol in small concentrations stimulates the ITPase activity as well as the ATPase activity of the "washed" salmon heart enzyme. However, in an enzyme preparation which had been freed of most of the bound nucleotides by dialysis in the presence of glycerol (Roveri et al., 1980) the ITPase activity is not stimulated by 2,4-dinitrophenol.     

B-型利尿钠肽在冠心病所致慢性充血性心力衰竭的诊断、治疗和愈后评估中的作用

冠心病的发病率在我国呈逐年上升的趋势,因冠心病心肌供血不足造成心肌损害最终导致心力衰竭。慢性心力衰竭特别是症状不典型的心力衰竭至今仍然是临床诊断上的一个难点,临床医生根据临床症状及体征所作出的诊断往往准确性偏低,应同时根据客观指标加以判断。BNP是近年来国内外研究的热点激素,在CHF的诊断、治疗和预后评估上受到广泛的重视,2003年被美国心脏病学会列为医学十大进展之一。本文就B-型利尿钠肽在冠心病所致慢性充血性心力衰竭的诊断、治疗和愈后评估中的作用作一全面的介绍。     

Rotation and asymmetric development of the zebrafish heart requires directed migration of cardiac progenitor cells

We have used high-resolution 4D imaging of cardiac progenitor cells (CPCs) in zebrafish to investigate the earliest left-right asymmetric movements during cardiac morphogenesis. Differential migratory behavior within the heart field was observed, resulting in a rotation of the heart tube. The leftward displacement and rotation of the tube requires hyaluronan synthase 2 expression within the CPCs. Furthermore, by reducing or ectopically activating BMP signaling or by implantation of BMP beads we could demonstrate that BMP signaling, which is asymmetrically activated in the lateral plate mesoderm and regulated by early left-right signals, is required to direct CPC migration and cardiac rotation. Together, these results support a model in which CPCs migrate toward a BMP source during development of the linear heart tube, providing a mechanism by which the left-right axis drives asymmetric development of the vertebrate heart.     

Effect of heart weight on distribution of lung surface pressures in vertical dogs

In head-up dogs the vertical gradient of transpulmonary pressure (VGTP) disappears after pneumothorax develops. Our laboratory recently confirmed that the heart moves downward and posteriorly with pneumothorax. To study the extent to which the heart is supported by the lungs, we used a linear elasticity model and finite-element analysis. The lung and heart were assumed to be symmetric along a vertical axis. Reported values of the elastic properties of lung and heart were assigned. The model was generated first without the heart, using the lung alone. The heart was then added to the model. Finally, heart weight was doubled. Adding the heart caused the VGTP to increase; doubling the heart weight further increased the VGTP. These increases were more pronounced at higher lung volumes. Lung inflation was accompanied by an upward displacement of the heart. Inclusion of the heart caused increased inhomogeneities in regional volume distribution. The effect of heart weight may in part explain why the VGTP in the head-up dog is greater than that predicted by lung density.     

Cardiomyocyte-endothelial cell control of lipoprotein lipase

In people with diabetes, inadequate pharmaceutical management predisposes the patient to heart failure, which is the leading cause of diabetes related death. One instigator for this cardiac dysfunction is change in fuel utilization by the heart. Thus, following diabetes, when cardiac glucose utilization is impaired, the heart undergoes metabolic transformation wherein it switches to using fats as an exclusive source of energy. Although this switching is geared to help the heart initially, in the long term, this has detrimental effects on cardiac function. These include the generation of noxious byproducts, which damage the cardiomyocytes, and ultimately result in increased morbidity and mortality. A key perpetrator that may be responsible for organizing this metabolic disequilibrium is lipoprotein lipase (LPL), the enzyme responsible for providing fat to the hearts. Either exaggeration or reduction in its activity following diabetes could lead to heart dysfunction. Given the disturbing news that diabetes is rampant across the globe, gaining more insight into the mechanism(s) by which cardiac LPL is regulated may assist other researchers in devising new therapeutic strategies to restore metabolic equilibrium, to help prevent or delay heart disease seen during diabetes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk.     

CFD simulation of flow through heart: a perspective review

The heart is an organ which pumps blood around the body by contraction of muscular wall. There is a coupled system in the heart containing the motion of wall and the motion of blood fluid; both motions must be computed simultaneously, which make biological computational fluid dynamics (CFD) difficult. The wall of the heart is not rigid and hence proper boundary conditions are essential for CFD modelling. Fluid-wall interaction is very important for real CFD modelling. There are many assumptions for CFD simulation of the heart that make it far from a real model. A realistic fluid-structure interaction modelling the structure by the finite element method and the fluid flow by CFD use more realistic coupling algorithms. This type of method is very powerful to solve the complex properties of the cardiac structure and the sensitive interaction of fluid and structure. The final goal of heart modelling is to simulate the total heart function by integrating cardiac anatomy, electrical activation, mechanics, metabolism and fluid mechanics together, as in the computational framework.     

The mouse as a model for heart morphogenesis in mammals: the origin of myocytes and studies with cardiac explants

The heart is one of the first organs to form during embryogenesis since its circulatory function is critical from early stages for embryo survival. In man, morphological events are affected by molecular perturbations, which can lead to a congenital heart defect. It is important therefore to understand not only the molecular signals, but also the morphological events, which govern myocardial cell identity. The study of transgenic mouse lines, Mlc1v-nlacZ-24 and Mlc3f-nlacZ-2, has led to the identification of a new precardiac territory, the anterior heart field, which has also been described recently in birds, and which contributes to the myocardium of the arterial pole of the heart. The use of explant cultures also indicates that pharyngeal mesoderm participates in the formation of the outflow tract and right ventricle and shows that the primitive heart tube has a predominantly left ventricular identity. We have also shown that Fgf-10 is expressed in the anterior heart field, where a role for FGF signaling in arterial pole morphogenesis is suggested by inhibitor experiments. Finally explant cultures have been employed to examine the acquisition of left-right atrial identity. The Mlc3f-nlacZ-2 line, which marks the right atrium, allowed us to determine the time window during which left-right signaling confers left-right atrial identity.     

Nodal蛋白的表达、纯化及多克隆抗体制备

斑马鱼心脏发育模型中Nodal编码转录因子调节心脏的左右不对称发育,为了进一步研究Nodal信号途径在心脏发育中的调控作用和心脏疾病发生的分子机制,需要获得斑马鱼Nodal蛋白并制备其抗体.采用从斑马鱼心脏组织中提取RNA,通过反转录得到心脏组织各种表达基因的cDNA为模板,PCR扩增得到Nodal部分编码区序列,然后将其连接到pET-28a载体上获得原核表达.经酶切及测序鉴定后,转化Rosseta细菌,并用IPTG诱导表达融合蛋白,Ni-IDA凝胶柱亲和纯化,将纯化的融合蛋白免疫新西兰大白兔制备多克隆抗体,并用Western blotting检测抗体.获得了Nodal原核表达重组融合蛋白及高效价的特异性兔抗Nodal多克隆抗体,为Nodal功能的进一步研究奠定了基础.     

Single neurone responses to tactile stimulation of the heart in the snail,Helix pomatia L.

Summary The electrical activity of the heart nerve and of single neurons in the suboesophageal ganglia were recorded during tactile stimulation of the heart. 15 neurons were identified which responded to heart stimulation by inhibiting or accelerating activity. Cells influenced by heart afferents are scattered in the visceral and in the right and left parietal ganglia.In most of the cases both decrease and increase of cell activity are caused by synaptic potentials, in some cases, however, the neuron is assumed to have a sensory character.The activity of three neurons influenced by heart stimulation was conducted into the heart nerve. These cells are central neurons of a heart-CNS-heart reflex.Some of the neurons located in the right parietal and visceral ganglia have no connection with the mechanoreceptors of the heart. Since their spikes propagate into the heart nerve, they probably take part in the extracardial regulation of heart activity.One of the neurons located in the visceral ganglion (cell V12) sends its axon into the heart nerve. The response of this neuron to heart stimulation was an increase in activity and an inhibition of the heart rate. This is an inhibitory neuron of the extracardial heart regulatory system.     

Disease modeling of desmosome-related cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes

Cardiomyopathy is a pathological condition characterized by cardiac pump failure due to myocardial dysfunction and the major cause of advanced heart failure requiring heart transplantation. Although optimized medical therapies have been developed for heart failure during the last few decades, some patients with cardiomyopathy exhibit advanced heart failure and are refractory to medical therapies. Desmosome, which is a dynamic cell-to-cell junctional component, maintains the structural integrity ...     

ANTICOAGULANT THERAPY IN HEART DISEASE—A Summary of the Literature

Considerable experience by many independent workers with the use of anticoagulants in the treatment of certain types of heart disease has shown that such therapy reduces significantly the incidence of thromboembolic complications and, largely through this effect, the morbidity and mortality rate from heart disease of these types.This is certainly established in acute coronary occlusion with myocardial infarction and in those instances of rheumatic heart disease with auricular fibrillation in which repeated embolic phenomena have occurred. The case for the administration of the anticoagulants in congestive heart failure is less secure, although there is no doubt that the number of thromboembolic complications is reduced by use of them.The administration of the anticoagulants requires considerably more exacting attention than does the administration of the majority of therapeutic agents in use commonly today. Hence, it is suggested that the use of anticoagulants in heart disease be restricted to those instances in which the indications are clear and facilities are compatible with the efficient and safe use of the drug, whether Dicumarol or heparin.     

The Chiral Looping of the Embryonic Heart Is Formed by the Combination of Three Axial Asymmetries

In mammals and birds, embryonic development of the heart involves conversion of a straight tubular structure into a three-dimensional helical loop, which is a chiral structure. We investigated theoretically the mechanism of helical loop formation of the mouse embryonic heart, especially focusing on determination of left-/right-handedness of the helical loop. In geometrical terms, chirality is the result of the combination of three axial asymmetries in three-dimensional space. We hypothesized the following correspondences between axial asymmetries and morphogenesis (bending and displacement): the dorsal-ventral asymmetry by ventral bending of a straight tube of the initial heart and the left-right and anterior-posterior asymmetries, the left-right asymmetry by rightward displacement of the heart tube, which is confined to the anterior region of the tube. Morphogenesis of chiral looping of the embryonic heart is a large-scaled event of the multicellular system in which substantial physical force operates dynamically. Using computer simulations with a cell-based physico-mechanical model and experiments with mouse embryos, we confirmed the hypothesis. We conclude that rightward displacement of the tube determines the left-handed screw of the loop. The process of helix loop formation consists of three steps: 1) the left-right biasing system involving Nodal-related signals that leads to left-right asymmetry in the embryonic body; 2) the rightward displacement of the tube; and finally 3) the left-handed helical looping. Step 1 is already established. Step 3 is elucidated by our study, which highlights the need for step 2 to be clarified; namely, we explore how the left-right asymmetry in the embryonic body leads to the rightward displacement of the heart tube.     

Ion transport by heart mitochondria. Retention and loss of energy coupling in aged heart mitochondria

The retention and loss of energy-coupling reactions in isolated beef heart mitochondria have been examined under anaerobic conditions using suspending media chosen to mimic the intracellular milieu. In long-term incubations at 37 °C, a loose coupling develops which can be controlled by adding serum albumin. This lesion closely resembles that produced by addition of free fatty acids which has been described in previous studies. Shorter incubation times produce an increased susceptibility to hydrogen peroxide which is characterized by elevated ATPase activity, increased permeability to monovalent cations, and increased proton ejection on transition from the anaerobic to the aerobic state. This peroxide sensitivity is prevented by chelators such as EGTA and appears to involve a time-dependent release of metal ions. Of the metabolites which are known to increase in concentration in the ischemic heart cell, Na⁺, P₁, lactate, and H⁺ all promote swelling of isolated heart mitochondria and contribute to a decline in energy coupling. The relationship of these results to the pathological deterioration of mitochondria in ischemic heart tissue is discussed.     

Aortic banding in rat as a model to investigate malnutrition associated with heart failure

Heart failure is a severe pathology, which has displayed a dramatic increase in the occurrence of patients with chronic heart disease in developed countries, as a result of increases in the population's average age and in survival time. This pathology is associated with severe malnutrition, which worsens the prognosis. Although the cachexia associated with chronic heart failure is a well-known complication, there is no reference animal model of malnutrition related to heart failure. This study was designed to evaluate the nutritional status of rats in a model of loss of cardiac function obtained by ascending aortic banding. Cardiac overload led to the development of cardiac hypertrophy, which decompensates to heart failure, with increased brain natriuretic peptide levels. The rats displayed hepatic dysfunction and an associated renal hypotrophy and renal failure, evidenced by the alteration in renal function markers such as citrullinemia, creatininemia, and uremia. Malnutrition has been evidenced by the alteration of protein and amino acid metabolism. A muscular atrophy with decreased protein content and increased amino acid concentrations in both plasma and muscle was observed. These rats with heart failure displayed a multiorgan failure and malnutrition, which reflected the clinical situation of human chronic heart failure.     

INDICATIONS FOR ANGIOCARDIOGRAPHY

Angiocardiography is indicated in selected cases of heart disease in which a definite diagnosis cannot be made by ordinary methods or in which there is reasonable expectation that the information so obtained may influence the treatment of the patient. Whenever possible, angiocardiography should be done in conjunction with cardiac catheterization. The main indication for angiocardiography is cyanotic congenital heart disease; primarily those cases in which there is a right-to-left shunt. Angiocardiography is occasionally of value in diagnosis of other types of congenital heart disease and in acquired heart disease.     

Heart development in normal and cardiac-lethal mutant axolotls: a model for the control of vertebrate cardiogenesis

The mechanisms which regulate myocardial differentiation are poorly understood. The cardiac-lethal (c) mutant of Ambystoma mexicanum, in which the heart never begins to beat, provides a valuable model system for studying this process. Using an in vitro assay, we examine the nature of the defect in c/c embryos and find (contrary to previous reports) that the inductive endoderm is not affected by the mutation. Rather, the pre-cardiac mesoderm is directly affected by the c gene and is incapable of responding to normal inductive influences. Furthermore, we find that mutant mesoderm can complete its differentiation into functional cardiomyocytes when co-cultured with wild-type heart mesoderm. With this evidence, we propose a model for the regulation of heart differentiation based on the migration of the heart mesoderm over a gradient of inducer, and the subsequent establishment of a two-component reaction-diffusion system within the mesoderm itself. This model has the potential to explain several poorly understood aspects of cardiogenesis, including the gradual nature of heart induction, the restriction of the heart field, and possibly the early morphogenesis of the heart tube.     

Anatomical position of heart in snakes with vertical orientation: a new hypothesis

It has been observed that climbing arboreal snakes have hearts closer to the head than nonclimbing terrestrial or aquatic snakes. The closeness to the head is said to minimize the work of the heart in pumping blood to the head. However, there is ample evidence that the gravitational pressure in the arteries going to the head is counterbalanced (neutralized) by the gravitational pressure of the blood in the veins going down to the heart. Hence, the heart does not do extra work so, another explanation must be sought. It is proposed that the position of the heart may be related to the filling pressure of the heart which is influenced by the compliance of the vessels above and below the heart. Some observations suggest that the caudal vessels in climbing snakes are less compliant than that of aquatic snakes. This tends to move the hydrostatic indifferent point closer to the head and provides an adequate filling pressure in climbing snakes in the vertical position.