Effects of Regulatory Peptides on Electrophysiological Properties of the Human Heart

During transesophageal electrical stimulation of the left atria in patients with heart diseases, an intravenous administration of Sandostatin prolonged the cardiac cycle and the effective refractory period of the atrioventricular junction, slowed down the sinoatrial conduction and the sinus node recovery time, and shifted the Wenckebach's point downwards. Neurotensin produced effects opposite to those of Sandostatin. During the Valsalva maneuver, Sandostatin strengthened bradycardia and broadened the range of heart rate changes associated with the vagal tone variations. The latter effect was also observed after the administration of neurotensin. Met-enkephalin and dalargin shortened the cardiac cycle, increased the corrected time of sinus node recovery time, but did not affect the cardiac rhythm dynamics during the Valsalva maneuver. These findings suggest that the regulatory peptides can be involved in control mechanisms determining the electrophysiological parameters of the human heart.     

Finger photoplethysmography during the Valsalva maneuver reflects left ventricular filling pressure

It is often challenging to assess cardiac filling pressure clinically. An improved system for detecting or ruling out elevated cardiac filling pressure may help reduce hospitalizations for heart failure. The blood pressure response to the Valsalva maneuver reflects left heart filling pressure, but its underuse clinically may be due in part to lack of continuous blood pressure recording along with lack of standardization of expiratory effort. In this study, we tested whether Valsalva-induced changes in the pulse amplitude of finger photoplethysmography (PPG), a technology already widely available in medical settings, correlate with invasively measured left ventricular end-diastolic pressure (LVEDP). We tested 33 subjects before clinically scheduled cardiac catheterizations. A finger photoplethysmography waveform was recorded during a Valsalva effort of 20 mmHg expiratory pressure sustained for 10 s, an effort most patients can achieve. Pulse amplitude ratio (PAR) was calculated as the PPG waveform amplitude just before release of expiratory effort divided by the waveform amplitude at baseline. PAR was well correlated with LVEDP (r = 0.68; P < 0.0001). For identifying LVEDP > 15 mmHG, PAR > 0.4 was 85% sensitive [95% confidence interval (95CI): 54-97%] and 80% specific (95CI: 56-93%). In conclusion, finger PPG, a technology already ubiquitous in medical centers, may be useful for assessing clinically meaningful categories of left heart filling pressure, using simple analysis of the waveform after a Valsalva maneuver effort that most patients can achieve.     

心脏的起源和细胞谱系

心脏是器官发生过程中最早形成的结构之一.心脏的原基分布图和心脏细胞谱系是心脏起源和形态发生研究的主要方面.总结了近几年来以鸡和小鼠为模型,在心脏发生和心脏前体细胞定位方面的研究情况.     

Pulse pressure response to the strain of the Valsalva maneuver in humans with preserved systolic function

Arterial pulsepressure response during the strain phase of the Valsalva maneuver hasbeen proposed as a clinical tool for the diagnosis of left heartfailure, whereas responses of subjects with preserved systolic functionhave been poorly documented. We studied the relationship between theaortic pulse amplitude ratio (i.e., minimum/maximum pulse pressure)during the strain phase of the Valsalva maneuver and cardiachemodynamics at baseline in 20 adults (42 ± 14 yr) undergoingroutine right and left heart catheterization. They were normal subjects(n = 5) and patients withvarious forms of cardiac diseases(n = 15), and all had a leftventricular ejection fraction 40%. High-fidelity pressures wererecorded in the right atrium and the left ventricle at baseline and atthe aortic root throughout the Valsalva maneuver. Aortic pulseamplitude ratio 1) did not correlatewith baseline left ventricular end-diastolic pressure, cardiac index(thermodilution), or left ventricular ejection fraction(cineangiography) and 2) waspositively related to total arterial compliance (area method) (r = 0.59) and to basal mean rightatrial pressure (r = 0.57) (eachP < 0.01). Aortic pulse pressureresponses to the strain were not related to heart rate responses duringthe maneuver. In subjects with preserved systolic function, the aorticpulse amplitude ratio during the strain phase of the Valsalva maneuver relates to baseline total arterial compliance and right heart fillingpressures but not to left ventricular function.

     

Cardiac shock wave therapy: assessment of safety and new insights into mechanisms of tissue regeneration

Although low-energy extracorporeal cardiac shock wave (ECSW) therapy represents an attractive non-invasive treatment option for ischaemic heart disease, the precise mechanisms of its action and influence on the cardiac tissue remain obscure. The goal of this study was to evaluate the effects of SW application on cardiac function and structure. Four-month-old Fisher 344 rats were subjected to ECSW therapy. Echocardiographic measurements of cardiac function were performed at baseline and at 1 and 3 months after treatment. Signs of inflammation, apoptosis and fibrosis were evaluated by immunohistochemistry in the control and treated hearts. ECSW application did not provoke arrhythmia or increase the troponin-I level. At all time points, the left ventricular ejection fraction and fractional shortening remained stable. Histological analysis revealed neither differences in the extracellular matrix collagen content nor the presence of fibrosis; similarly, there were no signs of inflammation. Moreover, a population of cardiac cells that responded eagerly to ECSW application in the adult heart was identified; c-kit-positive, Ki67-positive, orthochromatic cells, corresponding to cardiac primitive cells, were 2.65-fold more numerous in the treated myocardium. In conclusion, non-invasive ECSW therapy is a safe and effective way of activating cardiac stem cells and myocardial regeneration. Because many factors influence cellular turnover in the ischaemic myocardium during the course of ischaemic heart disease, cardiac remodelling, and heart failure progression, studies to identify the optimal treatment time are warranted.     

Recent advances in heart regeneration

Although cardiac stem cells (CSCs) and tissue engineering are very promising for cardiac regenerative medicine, studies with model organisms for heart regeneration will provide alternative therapeutic targets and opportunities. Here, we present a review on heart regeneration, with a particular focus on the most recent work in mouse and zebrafish. We attempt to summarize the recent progresses and bottlenecks of CSCs and tissue engineering for heart regeneration; and emphasize what we have learned from mouse and zebrafish regenerative models on discovering crucial genetic and epigenetic factors for stimulating heart regeneration; and speculate the potential application of these regenerative factors for heart failure. A brief perspective highlights several important and promising research directions in this exciting field. Birth Defects Research (Part C) 99:160–169, 2013. © 2013 Wiley Periodicals, Inc.     

Biophysical regulation during cardiac development and application to tissue engineering

Tissue engineering combines the principles of biology, engineering and medicine to create biological substitutes of native tissues, with an overall objective to restore normal tissue function. It is thought that the factors regulating tissue development in vivo (genetic, molecular and physical) can also direct cell fate and tissue assembly in vitro. In light of this paradigm, tissue engineering can be viewed as an effort of "imitating nature". We first discuss biophysical regulation during cardiac development and the factors of interest for application in tissue engineering of the myocardium. Then we focus on the biomimetic approach to cardiac tissue engineering which involves the use of culture systems designed to recapitulate some aspects of the actual in vivo environment. To mimic cell signaling in native myocardium, subpopulations of neonatal rat heart cells were cultured at a physiologically high cell density in three-dimensional polymer scaffolds. To mimic the capillary network, highly porous elastomer scaffolds with arrays of parallel channels were perfused with culture medium. To mimic oxygen supply by hemoglobin, culture medium was supplemented with an oxygen carrier. To enhance electromechanical coupling, tissue constructs were induced to contract by applying electrical signals mimicking those in native heart. Over only eight days of cultivation, the biomimetic approach resulted in tissue constructs which contained electromechanically coupled cells expressing cardiac differentiation markers and cardiac-like ultrastructure and contracting synchronously in response to electrical stimulation. Ongoing studies are aimed at extending this approach to tissue engineering of functional cardiac grafts based on human cells.     

Cardinal roles of miRNA in cardiac development and disease

MicroRNAs (miRNAs) are small noncoding RNAs that are emerging as pivotal modulators in virtually all aspects of cardiac biology, from cardiac development to cardiomyocyte survival and hypertrophy. The miRNA profiling, following gain- and loss-of-function studies using in vitro and in vivo models, has identified wide-ranging functions for miRNAs in the heart, providing new perspectives on their contributions to cardiac pathogenesis, and revealing potential therapeutic targets and diagnostic biomarkers. This review summarizes current progress in regulation of miRNAs in heart development and disease.     

Effect of PEEP on discharge of pulmonary C-fibers in dogs

Although positive end-expiratory pressure (PEEP) is believed to depress cardiac output and arterial pressure by compressing the vena cava and the heart, it is unclear whether PEEP also depresses these variables by a reflex arising from an inflation-induced stimulation of pulmonary C-fibers. We therefore recorded the impulse activity of 17 pulmonary C-fibers in barbiturate-anesthetized dogs with closed chests, while we placed the expiratory outlet of a ventilator under 5-30 cmH2O. Increasing PEEP in a ramp-like manner stimulated 12 of the 17 pulmonary C-fibers, with activity increasing from 0.0 +/- 0.1 to 0.9 +/- 0.2 imp/s when end-expiratory pressure equaled 15 cmH2O. When PEEP was increased in a stepwise manner to 15-20 cmH2O and maintained at this pressure for 15 min, pulmonary C-fibers increased their firing rates, but the effect was small averaging 0.2-0.3 imp/s after the 1st min of this maneuver. We conclude that pulmonary C-fibers are unlikely to be responsible for causing much of the decreases in cardiac output and arterial pressure evoked by sustained periods of PEEP in both patients and laboratory animals. These C-fibers, however, are likely to be responsible for causing the reflex decreases in these variables evoked by sudden application of PEEP.     

Measures of cardiac function in Theraphosidae spiders using in vivo magnetic resonance imaging

We report the first in vivo cardiac magnetic resonance imaging (MRI) measurements of Theraphosidae spiders. MRI scanning is performed on six spiders under isoflurane‐induced anaesthesia. Retrospective self‐gating cine‐cardiac MRI (RG‐CINE‐MRI) is used to overcome the difficulties of prospective cardiac gating in this species. The resulting RG‐CINE‐MRI images are successfully analyzed to obtain functional cardiac parameters from live spiders at rest. Cardiac ejection fraction is found to increase with animal mass (Pearson correlation 0.849, P = 0.03) at a faster rate than myocardial tissue volume, whereas heart rate remains constant across animals. This suggests the spider heart undergoes additional biomechanical loading with age. The results of the present study demonstrate the potential for retrospective gating with respect to evaluating aspects of cardiac function in a wide range of previously inaccessible species.     

G protein-coupled receptors in cardiac biology: old and new receptors

G protein-coupled receptors (GPCRs) are seven-transmembrane-spanning proteins that mediate cellular and physiological responses. They are critical for cardiovascular function and are targeted for the treatment of hypertension and heart failure. Nevertheless, current therapies only target a small fraction of the cardiac GPCR repertoire, indicating that there are many opportunities to investigate unappreciated aspects of heart biology. Here, we offer an update on the contemporary view of GPCRs and the complexities of their signalling, and review the roles of the ‘classical’ GPCRs in cardiovascular physiology and disease. We then provide insights into other GPCRs that have been less extensively studied in the heart, including orphan, odorant and taste receptors. We contend that these novel cardiac GPCRs contribute to heart function in health and disease and thereby offer exciting opportunities to therapeutically modulate heart function.     

The important role of catestatin in cardiac remodeling

Abstract

Catestatin (CST) was first discovered as a potent non-competitive and reversible inhibitor of catecholamine secretion. Recent reports on plasma CST level in heart diseases suggested a cardioprotective role for this peptide. Given that cardiac remodeling is the dominant pathologic process in cardiac dysfunction, we propose that CST participates in the regulation of concern pathways and contributes to the inhibition of cardiac remodeling. In this minireview, the potential mechanism of cardiac remodeling involving CST will be discussed from three aspects: hypertrophy, fibrosis, and apoptosis.     

Mesoderm progenitor cells of common origin contribute to the head musculature and the cardiac outflow tract

During early embryogenesis, heart and skeletal muscle progenitor cells are thought to derive from distinct regions of the mesoderm (i.e. the lateral plate mesoderm and paraxial mesoderm, respectively). In the present study, we have employed both in vitro and in vivo experimental systems in the avian embryo to explore how mesoderm progenitors in the head differentiate into both heart and skeletal muscles. Using fate-mapping studies, gene expression analyses, and manipulation of signaling pathways in the chick embryo, we demonstrate that cells from the cranial paraxial mesoderm contribute to both myocardial and endocardial cell populations within the cardiac outflow tract. We further show that Bmp signaling affects the specification of mesoderm cells in the head: application of Bmp4, both in vitro and in vivo, induces cardiac differentiation in the cranial paraxial mesoderm and blocks the differentiation of skeletal muscle precursors in these cells. Our results demonstrate that cells within the cranial paraxial mesoderm play a vital role in cardiogenesis, as a new source of cardiac progenitors that populate the cardiac outflow tract in vivo. A deeper understanding of mesodermal lineage specification in the vertebrate head is expected to provide insights into the normal, as well as pathological, aspects of heart and craniofacial development.     

Interrelationship between lactate and cardiac fatty acid metabolism

This overview is presented, in the main, to summarize the following aspects of lactate and cardiac fatty acid metabolism: 1. The utilization of exogenous carbohydrates and fatty acids by the heart. 2. The competition between lactate and fatty acids in cardiac energy metabolism. 3. The effect of lactate on endogenous triacylglycerol homeostasis. 4. Lactate-induced impairment of functional recovery of the post-ischemic heart. 5. The effect of lactate on lipid metabolism in the ischemic and post-ischemic heart. 6. The consequences of hyperlactaemia for cardiac imaging.     

Postnatal development of rat heart during 6-hydroxydopamine or propranolol treatment

Progressive postbirth development of mammalian heart contractile function is accompanied by augmentations of aerobic metabolic potential and cardiac myofibrillar ATPase activity. The temporal similarity of the above developmental sequences suggested that a single, unifying factor may coordinate myocardial maturation. It was hypothesized that cardiac sympathetic nervous system development might be regulating other aspects of myocardial growth. To test this hypothesis, previously well-defined aspects of heart metabolism and contractile protein ATPase activity were determined in rats which were either sympathectomized with 6-hydroxydopamine (6-OHDA) or subjected to chronic, beta-adrenergic blockade (propranolol) throughout the postbirth period from 3 to 6 weeks of age. Neither 6-OHDA treatment nor chronic, beta-adrenergic blockade resulted in a significant reduction of any metabolic enzyme specific activity or in myofibrillar ATPase. Myofibrillar creatine phosphokinase (CPK) activity underwent greater enhancement relative to ATPase during normal heart growth. Significant and divergent influences were exerted by 6-OHDA and propranolol drug regimens on myofibrillar CPK/ATPase enzyme activity ratio. These results indicate (a) the potential for independent regulation of myofibrillar CPK and ATPase, and (b) the advisability of evaluating CPK, ATPase, and CPK/ATPase enzymatic activities as myofibrillar correlates of heart contractile function. Nevertheless, the majority of developmentally related processes in the heart are minimally influenced by chemical sympathectomy.     

Cardiac differentiation of human pluripotent stem cells

Due to the extremely limited proliferative capacity of adult cardiomyocytes, human embryonic (pluripotent) stem cell derived cardiomyocytes (hESC-CMs) are currently almost the only reliable source of human heart cells which are suited to large-scale production. These cells have the potential for wide-scale application in drug discovery, heart disease research and cell-based heart repair. Embryonic atrial-, ventricular- and nodal-like cardiomyocytes can be obtained from differentiated human embryonic stem cells (hESCs). In recent years, several highly efficient cardiac differentiation protocols have been developed. Significant progress has also been made on understanding cardiac subtype specification, which is the key to reducing the heterogeneity of hESC-CMs, a major obstacle to the utilization of these cells in medical research and future cell-based replacement therapies. Herein we review recent progress in cardiac differentiation of hESCs and cardiac subtype specification, and discuss potential applications in drug screening and cell-based heart regeneration.     

Calsequestrin distribution, structure and function, its role in normal and pathological situations and the effect of thyroid hormones

Calsequestrin is the main calcium binding protein of the sarcoplasmic reticulum, serving as an important regulator of Ca(2+). In mammalian muscles, it exists as a skeletal isoform found in fast- and slow-twitch skeletal muscles and a cardiac isoform expressed in the heart and slow-twitch muscles. Recently, many excellent reviews that summarised in great detail various aspects of the calsequestrin structure, localisation or function both in skeletal and cardiac muscle have appeared. The present review focuses on skeletal muscle: information on cardiac tissue is given, where differences between both tissues are functionally important. The article reviews the known multiple roles of calsequestrin including pathology in order to introduce this topic to the broader scientific community and to stimulate an interest in this protein. Newly we describe our results on the effect of thyroid hormones on skeletal and cardiac calsequestrin expression and discuss them in the context of available literary data on this topic.     

Noninvasive electrocardiographic imaging for cardiac electrophysiology and arrhythmia

Over 7 million people worldwide die annually from erratic heart rhythms (cardiac arrhythmias), and many more are disabled. Yet there is no imaging modality to identify patients at risk, provide accurate diagnosis and guide therapy. Standard diagnostic techniques such as the electrocardiogram (ECG) provide only low-resolution projections of cardiac electrical activity on the body surface. Here we demonstrate the successful application in humans of a new imaging modality called electrocardiographic imaging (ECGI), which noninvasively images cardiac electrical activity in the heart. In ECGI, a multielectrode vest records 224 body-surface electrocardiograms; electrical potentials, electrograms and isochrones are then reconstructed on the heart's surface using geometrical information from computed tomography (CT) and a mathematical algorithm. We provide examples of ECGI application during atrial and ventricular activation and ventricular repolarization in (i) normal heart (ii) heart with a conduction disorder (right bundle branch block) (iii) focal activation initiated by right or left ventricular pacing, and (iv) atrial flutter.