Voltage-independent calcium release in heart muscle

The Ca2+ that activates contraction in heart muscle is regulated as in skeletal muscle by processes that depend on voltage and intracellular Ca2+ and involve a positive feedback system. How the initial electrical signal is amplified in heart muscle has remained controversial, however. Analogous protein structures from skeletal muscle and heart muscle have been identified physiologically and sequenced; these include the Ca2+ channel of the sarcolemma and the Ca2+ release channel of the sarcoplasmic reticulum. Although the parallels found in cardiac and skeletal muscles have provoked valuable experiments in both tissues, separation of the effects of voltage and intracellular Ca2+ on sarcoplasmic reticulum Ca2+ release in heart muscle has been imperfect. With the use of caged Ca2+ and flash photolysis in voltage-clamped heart myocytes, effects of membrane potential in heart muscle cells on Ca2+ release from intracellular stores have been studied. Unlike the response in skeletal muscle, voltage across the sarcolemma of heart muscle does not affect the release of Ca2+ from the sarcoplasmic reticulum, suggesting that other regulatory processes are needed to control Ca2(+)-induced Ca2+ release.     

柴胡对蟾蜍离体心脏功能活动影响的研究

[目的]观察不同浓度的柴胡水煮液对离体蟾蜍心脏活动的影响。[方法]采用斯氏离体蛙心灌流方法,分别以不同浓度的柴胡水煮液对离体的蟾蜍心脏进行灌流,经BL-420E生物机能实验系统记录离体蟾蜍心脏的收缩活动。[结果]0.009 g/ml的柴胡水煮液对离体蟾蜍心脏收缩振幅和心率影响均不明显（P〉0.05;P〉0.05）;而0.018 g/ml和0.180 g/ml的柴胡溶液对离体蟾蜍心脏收缩振幅和心率均具有降低与减慢的作用,影响显著（P〈0.01;P〈0.01）;尤其0.180 g/ml柴胡溶液对离体蟾蜍心脏的心肌收缩力的抑制作用更为明显,甚至导致心脏停止跳动。[结论]柴胡水煮液可抑制蟾蜍离体心脏的心肌收缩力,对心率有明显的减慢作用。     

Advanced cardiac morphogenesis does not require heart tube fusion

The bilateral cardiac mesoderm migrates from the lateral region of the embryo to the ventral midline, where it fuses to form the primitive heart tube. It is generally accepted that migration and fusion are essential for subsequent stages of cardiac morphogenesis. We present evidence that, in Foxp4 mutant embryonic mice, each bilateral heart-forming region is capable of developing into a highly differentiated four-chambered mammalian heart in the absence of midline fusion. These data demonstrate that left-right chamber specification, cardiac looping, septation, cardiac myocyte differentiation, and endocardial cushion formation are preprogrammed in the precardiac mesoderm and do not require midline positional identity or heart tube fusion.     

对慢性心衰心阳虚证及其微观指标关系的思考

本文通过对慢性心力衰竭心阳虚证症候特点、病程变化机制、血流动力学、心功能分级、心脏负荷标志物、神经内分泌相关激素、炎症反应物等相关指标的关联整理,研究其诊断价值,为病证结合慢性心力衰竭心阳虚证提供辅助诊断依据,并对心衰心阳虚证微观辨证发展现状进行反思。     

斑马鱼hoxb4a在心脏发育中的功能

斑马鱼转录因子hoxb4a在心脏中的功能未见研究报道,为了阐明hoxb4a在心脏发育中的作用,本文利用基因沉默技术和mRNA基因过表达方法,分别在斑马鱼中敲降和过表达hoxb4a基因,发现抑制或过表达hoxb4a的胚胎在第3天出现心包腔肿大、心脏环化异常的表型。通过原位杂交技术对野生型及hoxb4a敲降胚胎进行心肌特异基因的原位杂交染色比较,测量结果显示hoxb4a敲降胚胎的心脏环化角度增大（P<0.01）。接着利用转基因鱼系,发现敲降hoxb4a后的胚胎存在鳃弓异常、心内膜畸形的表型。进一步使用qPCR检测hoxb4a沉默后心脏相关基因的表达量变化, 结果显示 hoxb4a敲降后,多数心脏发育关键基因出现显著性下调,而调控心脏腔室分化的关键基因nppa明显上调（P<0.05）。本研究表明斑马鱼hoxb4a沉默会导致心脏结构畸形、环化异常,并且调控了早期心脏发育基因的变化。本研究发现了hoxb4a在斑马鱼早期心脏发育中发挥作用,并通过原位杂交及qPCR结果初步探索了hoxb4a调控心脏腔室的分化及心脏环化过程,深化了人们对心脏发育调控网络的认识。     

Rapid beta-adrenergic modulation of cardiac calcium channel currents by a fast G protein pathway

beta-Adrenergic agonists activate the G protein, Gs, which stimulates cardiac calcium currents by both cytoplasmic, indirect and membrane-delimited, direct pathways. To test whether beta-adrenergic agonists might use both pathways in the heart, isoproterenol was rapidly applied to cardiac myocytes, resulting in a biphasic increase in cardiac calcium channel currents that had time constants of 150 milliseconds and 36 seconds. beta-Adrenergic antagonists of a G protein inhibitor blocked both the fast and slow responses, whereas the adenylyl cyclase activator forskolin produced only the slow response. The presence of a fast pathway in the heart can explain what the slow pathway cannot account for: the ability of cardiac sympathetic nerves to change heart rate within a single beat.     

The embryonic vertebrate heart tube is a dynamic suction pump

The embryonic vertebrate heart begins pumping blood long before the development of discernable chambers and valves. At these early stages, the heart tube has been described as a peristaltic pump. Recent advances in confocal laser scanning microscopy and four-dimensional visualization have warranted another look at early cardiac structure and function. We examined the movement of cells in the embryonic zebrafish heart tube and the flow of blood through the heart and obtained results that contradict peristalsis as a pumping mechanism in the embryonic heart. We propose a more likely explanation of early cardiac dynamics in which the pumping action results from suction due to elastic wave propagation in the heart tube.     

活动平板试验配合心脏放射性核素检查诊断冠心病的价值（附53例报告）

对临床拟诊为冠心病５３例作活动平板试验并配合心核素检查的结果显示：双阳性２６例（４９．１％），平板试验阳性／心核素检查阴性４例（７．５％）；平板试验阴性／心核素检查阳性１４例（２６．４％）；双阴性９例（１７％）。表明双阳性可肯定冠心病的诊断，双阴性可否定诊断。平板试验阴性／心核素检查阳性，应结合临床做出诊断，平板试验阳性／心核素检查阴性为冠心病的危险因素，宜长期随诊。     

BRADYKININ: VASCULAR RELAXANT, CARDIAC STIMULANT

Bradykinin infusion causes an increase in cardiac output in rats whether the autonomic nervous system is blocked or not. After autonomic blockade, bradykinin causes a lesser decrease in the total peripheral resistance but a greater increase in cardiac output, resulting in an elevation of arterial pressure. The increase in cardiac output is caused by a small increase in heart rate and a substantial increase in stroke volume. The fact that these increases are observed after autonomic blockade suggests that bradykinin increases cardiac output by direct stimulation of the heart.     

Atrial natriuretic peptide elevation in congestive heart failure in the human

A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.     

慢性充血性心力衰竭患者血清心肌肌钙蛋白I和C-反应蛋白的变化

目的:探讨慢性充血性心力衰竭(CHF)患者心功能改善前后血清心肌肌钙蛋白I(cTnI)及C-反应蛋白(CRP)的变化及意义。方法:37例慢性充血性心力衰竭(NYHA分级Ⅲ~Ⅳ级)患者分别于入院d2和心功能改善至Ⅰ~Ⅱ级后抽取血清作cTnI、CRP测定。结果:治疗前患者血清cTnI阳性率54.1%,CRP超正常范围占78.4%。经治疗心功能改善后患者血清cTnI阳性率21.6%(P<0.01),CRP超正常范围占35.1%(P<0.01)。结论:部分慢性充血性心力衰竭患者心功能恶化时存在心肌损伤或坏死,此过程随心功能改善而改变,部分可能与其它因素有关。     

The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1

The early morphogenetic mechanisms involved in heart formation are evolutionarily conserved. A screen for genes that control Drosophila heart development revealed a cardiac defect in which pericardial and cardial cells dissociate, which causes loss of cardiac function and embryonic lethality. This phenotype resulted from mutations in the genes encoding HMG-CoA reductase, downstream enzymes in the mevalonate pathway, and G protein Ggamma1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell-autonomous requirement of Ggamma1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.     

Cardiac myosin activation: a potential therapeutic approach for systolic heart failure

Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase cardiac contractility indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin. Here, we show that it binds to the myosin catalytic domain and operates by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. Paradoxically, it inhibits adenosine 5'-triphosphate turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of contraction. Cardiac myosin activation may provide a new therapeutic approach for systolic heart failure.     

Normalization of depressed heart function in rats by ribose

Severe constriction of the abdominal aorta and simultaneous injection of isoproterenol in rats induced depression in heart function and reductions in cardiac adenosine triphosphate and total adenine nucleotides. When ribose was continuously infused for 24 hours, biosynthesis of cardiac adenine nucleotides was stimulated to such an extent that the reductions in adenosine triphosphate and total adenine nucleotides were prevented and left ventricular hemodynamic parameters were normal. These results support the hypothesis that adenosine triphosphate is primarily responsible for depression in myocardial contractility and that ribose is cardioprotective through its pronounced effects on adenine nucleotide metabolism in heart muscle.     

Cardiac activity preparatory to overt and covert behavior

The heart rates of 17 women subjects were recorded as they prepared to make both overt (key press) and covert (silently thinking the word "stop") responses. A very reliable preparatory cardiac response was obtained regardless of whether the overt or covert response mode was employed. The temporal development of this cardiac response faithfully reflected the speed with which the subjects were asked to respond, suggesting that in the covert condition heart rate could be used to detect the time at which a mental event was being generated.     

A single troponin T gene regulated by different programs in cardiac and skeletal muscle development

A cloned complementary DNA derived from a messenger RNA transiently present at low abundance levels in early chick embryonic skeletal muscle hybridizes to a messenger RNA present at high abundance levels in cardiac muscle. Genomic DNA hybridization and nucleotide sequence identity of complementary DNA's from both heart and skeletal muscle demonstrate that the messenger RNA's from both sources are encoded by the same gene. The encoded polypeptide is a troponin T sequence which is probably a cardiac isoform. This single copy troponin T isogene is governed by different regulatory programs in heart and skeletal muscle differentiation.     

Simple telemetering system for signaling high rumen pressures

The construction of a modified Hartley oscillator transmitter activated through a pressure switch is described. When this device is placed within the rumen of a cow which is allowed unrestricted movement in the pasture, frequency-modulation signals are transmitted to a recording receiver whenever a preselected pressure is exceeded. The pressure at which transmission begins is determined by the capacitance across the coil of the circuit.     

Control of stress-dependent cardiac growth and gene expression by a microRNA

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of alpha-myosin heavy chain (alphaMHC) and up-regulation of betaMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism. Thus, the alphaMHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.     

2只朱鹮死亡的病理学诊断

对２只死亡朱鹮进行了病理学检查。发现病例１，肝细胞变性，肺淤血，肾小管上皮细胞变性、坏死，间质出血，心肌纤维变性，间质出血，大脑出血，“卫星化”与“噬神经”现象，小脑浦肯野氏细胞坏死，还可见腺胃有大量的结核结节。病理学诊断为结核杆菌引起腹膜炎。病例２，肝细胞变性，肺淤血，肾小管上皮细胞变性、坏死，间质出血，心肌纤维变性，间质出血，肾、心、胰脏均可见到散在分布的球菌。病理学诊断为细菌感染引起败血症。     

In vitro studies of single isolated beating heart cells

Rat heart cells, separated by trypsin treatment and grown attached to glass in a liquid medium, exhibit periodic contractions similar to a whole beating heart. The rate of beating, which is up to 150 beats per minute, is affected by cardiac drugs and by metabolic substrates and inhibitors.