The looped heart does not save energy by maintaining the momentum of blood flowing in the ventricle

Previous studies suggested that the reconstruction or maintenance of physiological blood flow paths in the heart is important to obtain a good outcome following cardiac surgery, but this concept has no established theoretical foundation. We developed a multiscale, multiphysics heart simulator, based on the finite element method, and compared the hemodynamics of ventricles with physiological and nonphysiological flow paths. We found that the physiological flow path did not have an energy-saving effect but facilitated the separation of the outflow and inflow paths, so avoiding any mixing of the blood. The work performed by the ventricular wall was comparable at slower and faster heart rates (physiological vs. nonphysiological, 0.864 vs. 0.874 J, heart rate = 60 beats/min; and 0.599 vs. 0.590 J, heart rate = 100 beats/min), indicating that chiral asymmetry of the flow paths in the mammalian heart has minimal functional merit. At lower heart rates, the blood coming in the first beat was cleared almost completely by the ninth beat in both models. However, at high heart rates, such complete clearance was observed only in the physiological model, whereas 27.0% of blood remained in the nonphysiological model. This multiscale heart simulator provided detailed information on the cardiac mechanics and flow dynamics and could be a useful tool in cardiac physiology.     

Physiological responses to heat strain: A study on personal monitoring for young workers

Heart rate, increased body-core temperature and sweating are the physiological responses to heat stress and they are collectively known as physiological strain. Our goal was to study levels of physiological strain in young farm workers aged 15–21 y. We also verified that heart rate is the response that exceeds threshold limits earliest as seen in previous studies. Personal monitoring for heat-strain measures directly physiological strain as it occurs and gives further information about each worker's state. When estimating levels of physiological strain, certain limits concerning heart rate were adjusted considering the young ages of the workers studied.     

Genetic, environmental and maternal influences on embryonic cardiac rhythms

The relative roles of an animal's genetic constituents and environmental factors in influencing physiological variables such has heart rate have not been extensively investigated. This paper considers how heart rate patterns in the developing animal can be regulated, and how a combination of 'nature' and 'nurture' may interact to produce discrete patterns of heart rate change during development. The concept of the 'developmental trajectory' is evoked to generate a conceptual framework for how physiological development can be perturbed by environmental factors. Data are provided from three species showing how 'clutch-effects' (the fact that siblings perform physiologically much more similarly than non-siblings) can greatly influence the variance observed when collecting data on heart rate during development. Finally, so-called 'maternal effects', which are the influences on embryos of environmental experiences of the parents, are discussed as potentially confounding effects in the study of the genetic basis for physiological patterns of change during development.     

Learned Cardiac Control with Heart Rate Biofeedback Transfers to Emotional Reactions

Emotions involve subjective feelings, action tendencies and physiological reactions. Earlier findings suggest that biofeedback might provide a way to regulate the physiological components of emotions. The present study investigates if learned heart rate regulation with biofeedback transfers to emotional situations without biofeedback. First, participants learned to decrease heart rate using biofeedback. Then, inter-individual differences in the acquired skill predicted how well they could decrease heart rate reactivity when later exposed to negative arousing pictures without biofeedback. These findings suggest that (i) short lasting biofeedback training improves heart rate regulation and (ii) the learned ability transfers to emotion challenging situations without biofeedback. Thus, heart rate biofeedback training may enable regulation of bodily aspects of emotion also when feedback is not available.     

Distinct lipidomic profiles in models of physiological and pathological cardiac remodeling,and potential therapeutic strategies

Cardiac myocyte membranes contain lipids which remodel dramatically in response to heart growth and remodeling. Lipid species have both structural and functional roles. Physiological and pathological cardiac remodeling have very distinct phenotypes, and the identification of molecular differences represent avenues for therapeutic interventions. Whether the abundance of specific lipid classes is different in physiological and pathological models was largely unknown. The aim of this study was to determine whether distinct lipids are regulated in settings of physiological and pathological remodeling, and if so, whether modulation of differentially regulated lipids could modulate heart size and function. Lipidomic profiling was performed on cardiac-specific transgenic mice with 1) physiological cardiac hypertrophy due to increased Insulin-like Growth Factor 1 (IGF1) receptor or Phosphoinositide 3-Kinase (PI3K) signaling, 2) small hearts due to depressed PI3K signaling (dnPI3K), and 3) failing hearts due to dilated cardiomyopathy (DCM). In hearts of dnPI3K and DCM mice, several phospholipids (plasmalogens) were decreased and sphingolipids increased compared to mice with physiological hypertrophy. To assess whether restoration of plasmalogens could restore heart size or cardiac function, dnPI3K and DCM mice were administered batyl alcohol (BA; precursor to plasmalogen biosynthesis) in the diet for 16 weeks. BA supplementation increased a major plasmalogen species (p18:0) in the heart but had no effect on heart size or function. This may be due to the concurrent reduction in other plasmalogen species (p16:0 and p18:1) with BA. Here we show that lipid species are differentially regulated in settings of physiological and pathological remodeling. Restoration of lipid species in the failing heart warrants further examination.     

Discovery of multiple level heart-sound morphological variability resulting from changes in physiological states

Heart sounds carry information about the mechanical activity of the cardiovascular system. This information includes the specific physiological state of the subject, and short term variability related to the respiratory cycle. The interpretation of the sounds and extraction of changes in the physiological state, while monitoring short term variability is still an open problem and is the subject of this paper.We present a novel computational framework for analysis of data with multi-level variability, caused by externally induced changes. The framework presented includes an initial clustering of the first heart sound (S1) according to the morphology, and further aggregation of clusters into super-clusters. The clusters and super clusters are two methods of data segmentation, each reflecting a different level of variability in the data.The framework is applied to heart sounds recorded during laparoscopic surgeries of six patients. Procedures of this kind include anesthesia and abdominal insufflation, which together with the respiratory cycle, induce changes to the heart sound signal. We demonstrate a separation of the heart sound morphology according to different physiological states. The physiological states considered are the respiratory cycle, and the stages of the surgery. We achieve results of 90 ± 4% classification accuracy of heart beats to operation stages.The proposed framework is general and can be used to analyze data characterized by multi-level variability for various other (biomedical) applications.     

Analysis of various physiological salines for heart rate, CNS function, and synaptic transmission at neuromuscular junctions in Drosophila melanogaster larvae

Drosophila serves as a playground for examining the effects of genetic mutations on development, physiological function and behavior. Many physiological measures that address the effects of mutations require semi-intact or cultured preparations. To obtain consistent physiological recordings, cellular function needs to remain viable. Numerous physiological salines have been developed for fly preparations, with emphasis on nervous system viability. The commonly used saline drifts in pH and will cause an alteration in the heart rate. We identify a saline that maintains a stable pH and physiological function in the larval heart, skeletal neuromuscular junction, and ventral nerve cord preparations. Using these common assays, we screened various pH buffers of differing concentrations to identify optimum conditions. Buffers at 25 mM produce a stable heart rate with minimal variation in pH. Excitatory junction potentials evoked directly on larval muscles or through sensory-CNS-motor circuits were unaffected by at buffers at 25 mM. The salines examined did not impede the modulatory effect of serotonin on heart rate or neural activity. Together, our results indicate that the higher buffer concentrations needed to stabilize pH in HL3 hemolymph-like saline do not interfere with the acute function of neurons or cardiac myocytes.     

Regulation of adult and fetal myocardial phosphofructokinase. Relief of cooperativity and competition between fructose 2,6-bisphosphate, ATP, and citrate

To clarify the physiological role of fructose 2,6-bisphosphate in the perinatal switching of myocardial fuels from carbohydrate to fatty acids, the kinetic effects of fructose 2,6-bisphosphate on phosphofructokinase purified from fetal and adult rat hearts were compared. For both enzymes at physiological pH and ATP concentrations, 1 microM fructose 2,6-bisphosphate induced a greater than 10-fold reduction in S0.5 for fructose 6-phosphate and it completely eliminated subunit cooperativity. Fructose 2,6-bisphosphate may thereby reduce the influence of changes in fructose 6-phosphate concentration on phosphofructokinase activity. Based on double-reciprocal plots and ATP inhibition studies, adult heart phosphofructokinase activity is more sensitive to physiological changes in ATP and citrate concentrations than to changes in fructose 2,6-bisphosphate concentrations. Fetal heart phosphofructokinase is less sensitive to ATP concentration above 5 mM and equally sensitive to citrate inhibition. The fetal enzyme has up to a 15-fold lower affinity for fructose 2,6-bisphosphate, rendering it more sensitive to changes in fructose 2,6-bisphosphate concentration than adult heart phosphofructokinase. Together, these factors allow greater phosphofructokinase activity in fetal heart while retaining sensitive metabolic control. In both fetal and adult heart, fructose 2,6-bisphosphate is primarily permissive: it abolishes subunit cooperativity and in its presence phosphofructokinase activity is extraordinarily sensitive to both the energy balance of the cell as reflected in ATP concentration and the availability of other fuels as reflected in cytosolic citrate concentration.     

Tissue-specific modulation of the mitochondrial calcium uniporter by magnesium ions

This paper analyzes the kinetics of the Ca2+ uniporter of mitochondria from rat heart, kidney and liver operating in a range of Ca2+ concentrations near the steady-state value (1-4 microM). Heart mitochondria exhibit the lowest activity, and physiological Mg2+ concentrations inhibit the mitochondrial Ca2+ uniporter by approx. 50% in heart and kidney, and by 20% in liver. At physiological Ca2+ and Mg2+ concentrations the external free Ca2+ maintained by respiring mitochondria in vitro is higher in heart and kidney with respect to liver mitochondria. This behaviour could represent an adaptation of different mitochondria to their specific intracellular environment.     

Functional evaluation of the rat heart in situ.

We have developed methods for evaluating muscle function in the intact rat heart in situ using a contractility index (dP/dt)P-1, calculated from left ventricular pressure derivative-left ventricular pressure loop plots. Aortic flow measurements were also taken to further characterize in situ rat heart function. The preparation remained functionally stable and was within physiological blood gas and pH limits for at least 30 min following surgical procedures. The contractility index was not influenced by increased afterload, decreased preload or increased heart rate; however, appropriate changes were observed following isoproterenol and propranolol administration. Appropriate changes in aortic flow measurements were observed also with the above interventions. These studies demonstrate that the in situ rat heart is a stable physiological experimental preparation. It should be useful for evaluating heart function since a contractility index derived from pressure-velocity relationships and measurements necessary for pump function analysis can be obtained simultaneously.     

基于能量融合积分模型的心脏生理物理活动研究

为了更深入地了解目前靠生理实验及临床手段无法洞察的心脏三维空间的电生理运行机制,分析和表现心脏复杂的电生理活动,从而揭示心脏的生理物理特性,本研究通过人类心肌细胞的动作电位传导数学模型,结合基于心脏解剖数据所建立的真实心脏组织结构的三维空间模型,构建出精细的心脏生物物理融合模型,并将心脏在三维空间中的生物物理活动表现出来.实验结果表明,基于心脏动作电位传导的融合模型,不同时刻的动作电位传导在非匀质性组织内的三维空间中的传播位置、空间关系以及生物物理过程被清晰地显示出来,心脏研究人员从而能够以视觉感知的方式认识和深入理解人类心脏电生物物理系统的功能机制,并有助于进一步推测心脏的生理和病理反应.     

Increased uncoupling proteins and decreased efficiency in palmitate-perfused hyperthyroid rat heart

The physiological role of mitochondrial uncoupling proteins (UCPs) in heart and skeletal muscle is unknown, as is whether mitochondrial uncoupling of oxidative phosphorylation by fatty acids occurs in vivo. In this study, we found that UCP2 and UCP3 protein content, determined using Western blotting, was increased by 32 and 48%, respectively, in hyperthyroid rat heart mitochondria. Oligomycin-insensitive respiration rate, a measure of mitochondrial uncoupling, was increased in all mitochondria in the presence of palmitate: 36% in controls and 71 and 100% with 0.8 and 0.9 mM palmitate, respectively, in hyperthyroid rat heart mitochondria. In the isolated working heart, 0.4 mM palmitate significantly lowered cardiac output by 36% and cardiac efficiency by 38% in the hyperthyroid rat heart. Thus increased mitochondrial UCPs in the hyperthyroid rat heart were associated with increased uncoupling and decreased myocardial efficiency in the presence of palmitate. In conclusion, a physiological effect of UCPs on fatty acid oxidation has been found in heart at the mitochondrial and whole organ level.     

一种鸡胚胎心率记录的新方法

鸡胚胎是一种被广泛应用于发育生物学研究的实验材料。在以鸡胚胎为动物模型的各项研究工作中,心率常被看作是一个很重要的反应胚胎生理活动指标。本文详细介绍了一种侵入性的心电记录新方法,在正常的生理条件下通过记录鸡胚胎心电的变化来监测心率。首先在蛋壳上钻孔,将电极插入蛋内,然后通过放大器放大,A／D板转换,将心电信号输入电脑进行分析处理,提取与心率相关的信息。这种记录方式对胚胎损伤较小,不影响胚胎的正常发育;具有灵敏度高,操作简单,容易掌握等特点。     

Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy

Class I(A) phosphoinositide 3-kinases (PI3Ks) are activated by growth factor receptors, and they regulate, among other processes, cell growth and organ size. Studies using transgenic mice overexpressing constitutively active and dominant negative forms of the p110alpha catalytic subunit of class I(A) PI3K have implicated the role of this enzyme in regulating heart size and physiological cardiac hypertrophy. To further understand the role of class I(A) PI3K in controlling heart growth and to circumvent potential complications from the overexpression of dominant negative and constitutively active proteins, we generated mice with muscle-specific deletion of the p85alpha regulatory subunit and germ line deletion of the p85beta regulatory subunit of class I(A) PI3K. Here we show that mice with cardiac deletion of both p85 subunits exhibit attenuated Akt signaling in the heart, reduced heart size, and altered cardiac gene expression. Furthermore, exercise-induced cardiac hypertrophy is also attenuated in the p85 knockout hearts. Despite such defects in postnatal developmental growth and physiological hypertrophy, the p85 knockout hearts exhibit normal contractility and myocardial histology. Our results therefore provide strong genetic evidence that class I(A) PI3Ks are critical regulators for the developmental growth and physiological hypertrophy of the heart.     

有氧运动诱导心肌肥大和心肌细胞增殖的研究进展

适宜的运动负荷可刺激心肌生理性肥大和心肌细胞增殖,但这种内源性生理过程的分子机制知之甚少,因此有氧运动诱导心肌肥大和心肌细胞增殖的研究是目前发育生物学和细胞生物学领域的热点,其具体分子机制以及生理价值具有重要的生物学和医学研究及应用意义。该文综述了近年来有氧运动诱导心肌肥大和心肌细胞增殖的研究进展,旨在为相关领域的研究提供参考。     

Cryopreservation of human heart cells

Single cells were isolated from human heart specimens and preserved at -56 degrees C in a cryoprotecting solution containing dimethyl sulfoxide. The cells were reanimated by rapid thawing and the properties of the cells were evaluated in a physiological solution. The reanimated cells showed morphological and physiological properties similar to those seen in normal, freshly isolated cells. These results demonstrate the feasibility of storing human heart cells for long-term studies.     

Definitive assumption of heart function by the artificial heart

Reproducing the function of the natural heart with an artificial heart requires a multi-disciplinary approach. Problems to be solved are anatomical, physiological, biological and technical ones. Moreover, clinical use of the artificial heart on a large scale in the near future may involve economical, ethical and legal issues. These several aspects are reviewed, and the State of the Art in 1981 is established.     

自噬在疾病中的双重作用

自噬是细胞的一种正常的生理活动,参与细胞内损伤的蛋白质和亚细胞器经溶酶体途径降解的过程。自噬可以抵御外界的不良环境,在多种疾病中起着重要作用。近年来,大量研究表明自噬在细胞新陈代谢和生理功能上有双重作用,在疾病发生的不同时期,自噬起到不同的作用。通常情况自噬可以及时的清除细胞内损伤的蛋白质,作为一种细胞的保护机制,但是自噬的持续活化,导致细胞内大量蛋白质的降解,使细胞无法维持其基本结构,最终将导致细胞坏死或凋亡。自噬、凋亡和坏死的转化,很有可能受到p53、Bcl-2、Beclin-1、ATG5、TG2及p62等信号分子调控。肝脏和心脏是维持人体生命活动的重要器官,自噬在脂肪肝、肝硬化、心肌梗塞及心脏衰竭等疾病中扮演着重要的角色。本文总结了自噬、凋亡及坏死的相互关系,自噬在疾病中的双重作用,并重点介绍自噬在肝脏和心脏疾病中的作用。     

Low O2 avoidance is associated with physiological perturbation but not exhaustion in the snapper (Pagrus auratus: Sparidae)

It is already known that the New Zealand snapper (Pagrus auratus, Sparidae) does not avoid hypoxia until reaching an oxygen partial pressure (PO(2)) of 3.1±1.2 kPa at 18 °C. Avoidance at this level of PO(2) and temperature is below the critical oxygen partial pressure of the species (P(crit)=5.8±0.6 kPa, 43.5±4.5 mmHg) and is therefore expected to result in major physiological stress. Results from the current study showed that avoidance was associated with numerous physiological perturbations, including a significant endocrine response, haematological changes, osmoregulatory disturbance and metabolic adjustments in the heart, liver and muscle. Snapper clearly experienced physiological stress at the point of avoidance but they were not however in a state of physiological exhaustion since some fuel reserves were still available. In addition to avoidance, snapper also showed a subtle reduction in swimming speed - this energy-saving response may have helped snapper minimise the physiological challenge of low O(2) residence. It is therefore concluded that snapper can reside in water below their P(crit) threshold for brief periods of time and, without any evidence of physiological exhaustion at the point of avoidance, fish should recover quickly once normoxia is selected. Lastly, with signs of anaerobic metabolism in cardiac tissue at the point of avoidance, we tentatively suggest that snapper may leave hypoxia to protect heart function.