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Purpose: Idiopathic epicardial ventricular arrhythmias (VAs) are clustered in the areas of the summit and crux. This study was to report a group of idiopathic epicardial VAs remote from the summit and crux areas. Methods: In total, 9 patients (6 males, mean age 32 ± 13 years) were enrolled. The locations were identified by epicardial mapping and ablation. The electrocardiographic and electrophysiological characteristics were compared to those of 9 patients who had VAs ablated at the opposite endocardial site. Results: VAs were identified at the epicardium, with 4 patients had VAs located at the inferior wall, one at the anterior wall, one at the apex and 3 patients had VAs at the lateral wall. A "QS" type at the location-related leads was the only identified surface electrocardiogram indication suggesting epicardial origin (compared to that of the controls, 100% vs 0%, p<0.001). Endocardial and epicardial mapping revealed pre-maturities of −11 ± 4 ms and −25 ± 8 ms, respectively (VS. −28 ± 8 ms revealed by endocardial mapping in control patients, p<0.001 and p=0.389, respectively). All of the study cases demonstrated an "rS" pattern in the endocardial unipolar electrogram. Acute and long-term successful ablation (a median of 11 months of follow-up) was achieved in all patients without complications. Conclusions: A distinct group of idiopathic VAs remote from the summit and crux areas warranting ablation by a subxiphoid approach were identified. Morphological ECG features of a "QS" type among the location-related grouped leads combined with the mapping findings helped in the identification of the epicardial site of origin. [ABSTRACT FROM AUTHOR]

Lower invertebrates' hearts such as those of zebrafish have the capacity for scarless myocardial regeneration which is lost by mammalian hearts as they form a fibrotic scar tissue instead of regenerating the injured area. However, neonatal mammalian hearts have a remarkable capacity for regeneration highlighting conserved evolutionary mechanisms underlying such a process. Studies investigated the underlying mechanism of myocardial regeneration in species capable to do so, to see its applicability on mammals. The epicardium, the mesothelial outer layer of the vertebrate heart, has proven to play an important role in the process of repair and regeneration. It serves as an important source of smooth muscle cells, cardiac fibroblasts, endothelial cells, stem cells, and signaling molecules that are involved in this process. Here we review the role of the epicardium in myocardial regeneration focusing on the different involved; Activation, epithelial to mesenchymal transition, and differentiation. In addition, we will discuss its contributory role to different aspects that support myocardial regeneration. Of these we will discuss angiogenesis and the formation of a regenerate extracellular matrix. Moreover, we will discuss several factors that act on the epicardium to affect regeneration. Finally, we will highlight the utility of the epicardium as a mode of cell therapy in the treatment of myocardial injury. [ABSTRACT FROM AUTHOR]

If viewed as a movie, heart morphogenesis appears to unfold in a continuous and seamless manner. At the mechanistic level, however, a series of discreet and separable processes sequentially underlie heart development. This is evident in examining the expansion of the ventricular wall, which accounts for most of the contractile force of each heartbeat. Ventricular wall expansion is driven by cardiomyocyte proliferation coupled with a morphogenetic program that causes wall thickening rather than lengthening. Although most studies of these processes have focused on heart-intrinsic processes, it is increasingly clear that extracardiac events influence or even direct heart morphogenesis. In this review, we specifically consider mechanisms responsible for coordinating cardiomyocyte proliferation and ventricular wall expansion in mammalian development, relying primarily on studies from mouse development where a wealth of molecular and genetic data have been accumulated. [ABSTRACT FROM AUTHOR]

We herein describe a case of VT in an ischemic cardiomyopathy patient utilizing a novel technique of simultaneous endo-epicardial high-density mapping. Epicardial access, in addition to retrograde aortic endocardial access, was performed. Following the creation of the respective endocardial and epicardial electrical substrate maps, activation mapping of the VT was then performed simultaneously with two overlapping HD Grid catheters. Full diastolic pathway mapping was achieved, with EGMs recorded in all segments of the diastolic interval, on the epicardial surface. This case highlights the feasibility of a technique that can reliably detect the presence of activation bridges in a 3D model of VT. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the role of lipolysis of epicardial adipose tissue (EAT) in cardiac function after myocardial infarction (MI).Methods: We used a rat model of MI with or without EAT removal to study the effects of EAT lipolysis on cardiovascular function. Echocardiography and cardiac catheterization were used to determine cardiac function, and infarct size and histopathology specimens were analyzed in postmortem sections. Inflammatory responses were evaluated via flow cytometry and Elisa analyses.Results: We found that the lipolysis of EAT increased significantly after MI. Removal of the EAT after MI (MI-EAT) improved cardiac function by nearly 10% and decreased the infarct area by 6% when compared with rats retaining EAT after MI (MI+EAT). Furthermore, the removal of EAT reduced the number of CD45-positive leukocytes (50 vs. 34.8%) and increased the ratio of macrophage/leukocytes (56 vs. 75%) in the infarcted heart. Compared with the MI+EAT group, the concentration of tumor necrosis factor-alpha and interleukin 1‑beta were reduced in the MI-EAT group.Conclusion: Lipolysis of EAT increased significantly after MI. Removal of EAT improved cardiac function, in part, by weakening the inflammatory response. [ABSTRACT FROM AUTHOR]

Cardiomyocyte (CM) differentiation from proepicardial organ- (PEO) and embryonic epicardium (eEpi)-derived cells or EPDCs in a developing heart emerges as a wide interest in purview of cardiac repair and regenerative medicine. eEpi originates from the precursor PEO and EPDCs, which contribute to several cardiac cell types including smooth muscle cells, fibroblasts, endothelial cells, and CMs during cardiogenesis. Here in this report, we have analyzed several cardiac lineage-specific marker gene expressions between PEO and eEpi cells. We have found that PEO-derived cells show increased level of CM lineage-specific marker gene expression compared to eEpi cells. Moreover, Wnt signaling activation results in increased level of CM-specific marker gene expression in both PEO and eEpi cells in culture. Interestingly, Wnt signaling activation also increases the number of proliferating and sarcomeric myosin (Mf20)-positive cells in eEpi explant culture. Together, this data suggests that eEpi cells as a source for CM differentiation and Wnt signaling mediator, β-catenin, might play an important role in CM differentiation from eEpi cells in culture. [ABSTRACT FROM AUTHOR]

Information about embryonic development of coronary endothelium is the main clue for the creation of new methods in tissue engineering for treatment of ischemic heart diseases. The purpose of the research was to describe human coronary vessels development on early stages of the prenatal ontogenesis. The first step in human coronary vessels development is the formation of endothelium de novo by transformation of some epicardial and, possibly, endocardial cells. The next step is the ingrowth of sinus venosus endothelium in subepicardium over ventricles and atria, which gives rise to the coronary vessels. Only after 7 days does the primitive coronary plexus of the heart communicate with aorta (third step). During this period, some subepicardial vessels invade myocardium and some intramyocardial vessels contact with the heart cavity. Such intercommunications could help in regulation of blood circulation in primitive coronary plexus before establishment of effective contacts between arterial and venous vessels-excess of blood could be discharged directly into the heart cavity. Additional population of CD34+ cells were revealed inside condensed mesenchyme of the conotruncus; it participates in the formation of vasa vasorum in the aorta. Epicardium and sinus venosus generate endothelium of coronary vessels by neovasculo- and angiogenesis, respectively. During a week after ingrowth of vessels from SV and before their ingrowth to the aorta, ventriculo-coronary communications could be found in the heart. [ABSTRACT FROM AUTHOR]

Patients with ischemic and non-ischemic cardiomyopathy often have substrate for ventricular tachycardia (VT) in the endocardium (ENDO), epicardium (EPI), and/or intramural. Although it has been reported that the ENDO unipolar (UNI) voltage map is useful in detecting EPI substrate, its feasibility to detect intramural scarring and its usefulness in radiofrequency catheter ablation (RFCA) remain unclear. To assess the relationship between the left ventricle (LV) ENDO UNI voltage map and the LV EPI bipolar (BIP) voltage map, and to determine the usefulness of the ENDO UNI voltage map to guide RFCA for VT in patients with cardiomyopathy undergoing combined ENDO- and EPI RFCA. Eleven patients with VT undergoing detailed ENDO and EPI electroanatomical mapping of the LV were included (mean age 59 ± 11 years, 9 men). We assessed the value of the LV ENDO UNI voltage map in identifying EPI and/or intramural substrate in these 11 patients with non-ischemic or ischemic cardiomyopathy. The underlying heart disease was dilated cardiomyopathy in 4 patients, cardiac sarcoidosis in 3, hypertrophic cardiomyopathy in 2, and ischemic heart disease in 2 patients. The mean LV ejection fraction was 24 ± 7 %. The low voltage zone (LVZ) was defined as <1.5 mV for LV ENDO BIP electrograms (EGMs), <8.3 mV for LV ENDO UNI EGMs, and <1.0 mV for LV EPI BIP EGMs. The surface area of each LVZ was measured. We also measured the LVZ of the spatial overlap between ENDO UNI and EPI BIP voltage maps using the transparency mode on CARTO software. We performed RFCA at the ENDO and EPI based on activation and/or substrate maps, targeting the LVZ and/or abnormal EGMs. The LVZ was present in the LV ENDO BIP voltage map in 10 of 11 patients (42 ± 33 cm), and in the LV ENDO UNI voltage map in 10 of 11 patients (72 ± 45 cm). The LVZ was present in the EPI BIP voltage map in 9 of 11 patients (70 ± 61 cm), and the LVZ in the ENDO UNI voltage map was also seen in all 9 patients. The location of the LVZ in the EPI BIP map matched that in 45 ± 28 % of ENDO UNI voltage maps. The LVZ in the ENDO UNI voltage map was larger than that in the EPI BIP voltage map in 6 of 11 patients, and RFCA failed in 5 of these 6 patients. In the remaining 5 patients with a smaller LVZ in the ENDO UNI voltage map compared with the EPI BIP voltage map or no LVZ both at ENDO UNI and EPI BIP voltage map, VT was successfully eliminated in 4 of 5 patients. The LV ENDO UNI voltage map is useful in detecting EPI substrate in patients with cardiomyopathy. A larger LVZ in the ENDO UNI voltage map compared to that in the EPI BIP voltage map may indicate the presence of intramural substrate, which leads to difficulty in eliminating VT, even with combined ENDO- and EPI RFCA. [ABSTRACT FROM AUTHOR]

A method of invasive and non-invasive examination of epicardial motion was tested on domestic pigs ( n=15). The invasive study employed a contact kinematic sensor of the epicardial wall motion, which determined the amplitude, velocity, and angular parameters of examined epicardial region. A non-invasive assessment of the epicardial kinematics based on echocardiographic 2D Velocity Vector Imaging and ECG recoding used to determine the heart electrical axis. The 4-chamber views were uses to analyze the longitudinal displacements of lateral wall of the left ventricle at the basal, mid, and apical segments. In addition, the radial displacements were determined in short axis projections at basal and apical segments as well as at the level of papillary muscles. The animals with normal or horizontal heart's electrical axis demonstrated similar displacement of the epicardium along X-axis and in longitudinal direction, while displacement along Y-axis corresponded to that in radial direction. The combined invasive and non-invasive approach in measurement of epicardium motion makes it possible to quantify the kinematic epicardial activity. [ABSTRACT FROM AUTHOR]

The epicardial halo delineates the heart shadow in fluoroscopy. To establish whether the sign is applicable to pericardiocentesis guidance, three investigators evaluated its intensity as absent = grade 0, indistinct = 0.5, clear = 1, intensive = 2 in posterior-anterior (PA) and lateral fluoroscopies recorded before pericardiocentesis or cardiac catheterization (Philips Integris-II BH3000). Three populations were studied: (a) 32 patients with pericardial effusion (PE group), 53.1 % males, aged 53.9 ± 13.9 years; (b) 14 patients with perimyocarditis (PM group), 64.3 % males, aged 51.6 ± 14.4 years; and (c) 46 coronary patients (CAD group), no PE, 95.6 % males, aged 67.3 ± 11.8 years. The intensity of the halo phenomenon was highest in patients with PE, lowest in patients with CAD, and intermediate in patients with PM (median sum of grades in PA/lateral view: 4/5 vs. 2/2.5 vs. 3/3, respectively) ( p < 0.01). The halo phenomenon correlated well with HR and echocardiographic PE size in both angiographic views. The correlation with body mass index (BMI) and age was significant only in the lateral view and with PE volume only in the PA view. The sensitivity of the halo sign for PE was 84.1 % in PA and 92.0 % in lateral views. In 10/32 PE patients, the evaluation of the sign was repeated after PE drainage, revealing lower grades both in PA and in lateral views ( p < 0.01). In conclusion, the epicardial halo sign is highly sensitive for the detection of a PE; it correlates well in at least one angiographic projection with the PE volume, HR, age, BMI, and the PE size in echocardiography and could be therefore applied as a safety guide for pericardiocentesis. [ABSTRACT FROM AUTHOR]

Recent reports indicate that the adult mammalian heart is capable of limited, but measurable, cardiomyocyte turnover. While the lineage origin of the newly formed cardiomyocytes is not entirely understood, mounting evidence suggest that the epicardium and subepicardium may represent an important source of cardiac stem or progenitor cells. Stem cell niches are characterized by low oxygen tension, where stem cells preferentially utilize cytoplasmic glycolysis to meet their energy demands. However, it is unclear if the heart harbors similar hypoxic regions, or whether these regions house metabolically distinct cardiac progenitor populations. Here we identify the epicardium and subepicardium as the cardiac hypoxic niche-based capillary density quantification, and localization of Hif-1α in the uninjured heart. We further demonstrate that this hypoxic microenvironment houses a metabolically distinct population of glycolytic progenitor cells. Finally, we show that Hif-1α regulates the glycolytic phenotype and progenitor properties of these cells. These findings highlight important anatomical and functional properties of the epicardial and subepicardial microenvironment, and the potential role of hypoxia signaling in regulation of cardiac progenitors. [ABSTRACT FROM AUTHOR]

Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGFβ) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGFβ-induced EMT is dependent on type-1 TGFβ receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha ( Pdgfrα), Snai1 and VCAM- 1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair. [ABSTRACT FROM AUTHOR]

Regular exercise can lead to electrical remodelling of the heart. The cellular mechanisms associated with these changes are not well understood, and are difficult to study in human tissue but are important given that exercise is recommended to the general population. We have investigated the role played by the transient outward K+ current ( Ito) in the changes in electrical activity seen in response to voluntary exercise training in rats. Female rats undertook 6 weeks of voluntary wheel running exercise (TRN) or were sedentary controls (SED). Monophasic action potentials (MAPs) were recorded from the surface of whole hearts. Whole cell patch clamp recordings of Ito; mRNA and protein levels of selected targets in sub-epicardial (EPI) and sub-endocardial myocardium of SED and TRN hearts were compared. In TRN rats, heart weight:body weight was significantly increased and epicardial MAPs significantly prolonged. Ito density was reduced in TRN EPI myocytes, such that the transmural gradient of Ito was significantly reduced ( P < 0.05). Computer modelling of these changes in Ito predicted the observed changes in action potential profile. However, transmural gradients in mRNA and protein expression for Kv4.2 or mRNA levels of the Kv4.2 regulators; KChIP2 and Irx-5 were not significantly altered by voluntary exercise. We conclude that voluntary exercise electrical remodelling is caused, at least in part, by a decrease in EPI Ito, possibly because of fewer functional channels in the membrane, which results in a fall in the transmural action potential duration gradient. [ABSTRACT FROM AUTHOR]

The epicardium is a critical tissue that directs several aspects of heart development, particularly via the secretion of soluble factors. This review summarizes recent approaches that implicate the epicardium as the source of mitogenic factors promoting cardiomyocyte proliferation, as the source of instructive signals that direct compact zone organization (morphogenesis), and as the tissue that directs formation of the coronary vasculature. [ABSTRACT FROM AUTHOR]

During cardiogenesis, the epicardium grows from the proepicardial organ to form the outermost layer of the early heart. Part of the epicardium undergoes epithelial-mesenchymal transformation, and migrates into the myocardium. These epicardium- derived cells differentiate into interstitial fibroblasts, coronary smooth muscle cells, and perivascular fibroblasts. Moreover, epicardium-derived cells are important regulators of formation of the compact myocardium, the coronary vasculature, and the Purkinje fiber network, thus being essential for proper cardiac development. The fibrous structures of the heart such as the fibrous heart skeleton and the semilunar and atrioventricular valves also depend on a contribution of these cells during development. We hypothesise that the essential properties of epicardium-derived cells can be recapitulated in adult diseased myocardium. These cells can therefore be considered as a novel source of adult stem cells useful in clinical cardiac regeneration therapy. [ABSTRACT FROM AUTHOR]

We evaluated whether pericardial injections of the retrograde tracers cholera toxin subunit B (CTb) or Fast Blue (FB) reliably labelled cardiac vagal pre-ganglionic neurons. Injections of CTb into the pericardial space of the rat labelled neurons in both the external and compact formations of the nucleus ambiguus. Most labelled neurons were found in the compact formation of the nucleus ambiguus, and the majority of these, and only these, expressed immunoreactivity for calcitonin gene-related peptide. This distribution of labelled neurons and their immunohistochemical properties is characteristic of oesophageal motoneurons. Examination of the oesophagus following intra-pericardial CTb applications revealed strong labelling of motor end plates within the skeletal muscle of the thoracic but not the abdominal oesophagus. When a second retrograde tracer, FB, was injected into the abdominal oesophagus, labelled somata were found adjacent to CTb-labelled neurons in the compact formation of the nucleus ambiguus. No co-localisation of tracers was found, but identical proportions of calcitonin gene-related peptide (CGRP) immunoreactivity were observed in both groups of neurons. FB injected into the pericardial space labelled intra-cardiac neurons but not brainstem neurons. We conclude that intra-pericardial, and perhaps sub-epicardial, injections of some retrograde tracers are likely to label a subset of oesophageal, as well as cardiac, vagal motor neurons in the brainstem. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare the distribution of ion currents and the major underlying ion channel proteins in canine and human subepicardial (EPI) and midmyocardial (MID) left-ventricular muscle. Ion currents and action potentials were recorded from canine cardiomyocytes derived from the very superficial EPI and central MID regions of the left ventricle. Amplitude, duration and the maximum velocity of depolarization of the action potential were significantly greater in MID than EPI myocytes, whereas phase-1 repolarization was more pronounced in the EPI cells. Amplitudes of the transient outwards K+ current (29.5±1.5 vs. 19.0±2.3 pA/pF at +50 mV) and the slow component of the delayed rectifier K+ current (10.3±2.3 vs. 6.5±1.0 pA/pF at +50 mV) were significantly larger in EPI than in MID myocytes under whole-cell voltage-clamp conditions. The densities of the inwards rectifier K+ current, rapid delayed rectifier K+ current and L-type Ca2+ current were similar in both cell types. Expression of channel proteins in both canine and human ventricular myocardium was determined by Western blotting. In the canine heart, the expression of Kv4.3, Kv1.4, KChIP2 and KvLQT1 was significantly higher, and that of Nav1.5 and MinK much lower, in EPI than in MID. No significant EPI-MID differences were observed in the expression of the other channel proteins studied (Kir2.1, α1C, HERG and MiRP1). Similar results were obtained in human hearts, although the HERG was more abundant in the EPI than in the MID layer. In the canine heart, the EPI-MID differences in ion current densities were proportional to differences in channel protein expression. Except for the density of HERG, the pattern of EPI-MID distribution of ion-channel proteins was identical in canine and human ventricles. [ABSTRACT FROM AUTHOR]

T-box genes encode transcription factors that control the development of diverse tissues and organs in vertebrate embryos. Here, we report the expression of the TBX18 gene during chick development. TBX18 expression is found in anterior halves of prospective and definitive somites as well as in the unsegmented cranial region of the paraxial mesoderm. Expression levels are high in the presomitic mesoderm but decrease in newly formed somites. This is in contrast to the mouse where uniform expression has been reported in the paraxial mesoderm. TBX18 expression is also prominent in the proepicardial serosa and in the epicardium of the heart. Other sites of expression include the genital ridge and the developing limb buds. [ABSTRACT FROM AUTHOR]

To understand how to reinitiate cell division in adult human myocardium, a heart regeneration model was examined in the amphibian axolotl salamander, Amblystoma mexicanum. The ventricular apex was surgically amputated and resected for 3 weeks. At 14 days of recovery, the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) was injected intraperitoneally to identify cell types undergoing S-phase by indirect immunofluorescence using primary anti-BrdU antibodies. This is the first report showing a concentrated area of cell division in the ventricle and cells throughout the atrial epicardium by confocal microscopic image analysis in response to wounding of the ventricle. Tissues coimmunostained with anti-BrdU and sarcomeric myosin-specific MF20 antibodies showed 12.8 ± 4.10% of myocytes contained BrdU+ nuclei in a 75 µm to 750 µm zone in the ventricular myocardium subjacent to the amputation plane. BrdU+ nuclei also were present in newly formed ventricular epicardium that surround dividing myocytes, and in epicardial mesothelium (74.3 ± 6.36 %) and connective tissue (44.9 ± 13.31%) cells distal to the wound. Unexpectedly, immunofluorescent BrdU+ nuclei were observed in isolated atrial myocytes (13.9 ± 1.45%) and in uninjured atrial epicardial mesothelium (64.3 ± 1.55%) and connective tissue (29.4 ± 5.50%). No BrdU+ nuclei were present in cardiomyocytes or epicardium from sham-operated and BrdU-treated controls. These results suggest that renewed cell division is a specific response to wounding of the ventricle. Additionally, release of a growth factor may be responsible for the specific localized mitotic ventricular cardiomyocyte response adjacent to the wound, and the more generalized atrial proliferative response distal to the amputation. [ABSTRACT FROM AUTHOR]

Distributions of epicardial potentials, calculated from body surface electrocardiograms (ECGs), were investigated to determine if they could enable detection of multiple sites of ventricular activity. An anatomical model of the human ventricular myocardium was used to simulate activation sequences initiated at nine different ventricular pairs of sites. From these sequences, body surface ECGs were simulated at 352 sites on the torso surface and then used to reconstruct epicardial potentials at 202 sites. The criterion for detection of dual ventricular events was the presence of two distinct primary potential minima in the reconstructed epicardial potentials. The shortest distance between the two events in the right ventricle that resulted in the reconstruction of epicardial potential patterns, featuring two minima, was 27 mm; the distance between the two events in the left ventricle was 23 mm. When Gaussian white noise in the simulated body surface potentials was increased from 3 microV to 15 microV and 50 microV, dual events became more difficult to distinguish. Findings indicate that calculated epicardial potentials provide useful visual information about the presence of multiple ventricular events that is not apparent in features of body surface ECGs, and could be particularly helpful in optimising mapping procedures during difficult or unsuccessful radiofrequency ablations of accessory pathways. [ABSTRACT FROM AUTHOR]

The purpose of the study was to determine whether a newKATP channel opener, Y 26763 (Y), can influence theelectrophysiological properties in the ischemic myocardium as well as todetermine whether the blunting effect of the α1-adrenoceptorantagonist bunazosin (BN) on an ischemia-induced shortening of repolarizationtime can be related to the KATP channel activity. The anteriordescending branch of the left coronary artery was ligated four times for 5minutes, separated by 15 minutes of reperfusion (stages 1–4) to testthe dose-dependent effect of drugs on repolarization. Dogs received eithervehicle (n = 9), Y (0.4, 2.0, and 4.0 μg/kg at stages 2, 3, and 4,respectively, with 0.4 μg/kg/min drip infusion at each of stages2–4, n = 7), BN (0.1 mg at each of stages 2–4, n =8), or a combination of these two drugs (BN + Y, the same dose of BNand Y in groups BN and Y, respectively, n = 9). Drugs wereadministered into the left atrium. The monophasic action potential (MAP)and regional electrograms were recorded. The MAP90 and theduration of the slow deflections (DSD) of the regional electrogram were usedas markers of repolarization. The Vmax of the MAP and the rapiddeflections (DRD) of the regional electrogram were used as markers ofconduction. Y augmented an ischemia-induced shortening of MAP90and DSD in proportion to an increase in the dose given and the plasmaconcentration ( P < .05–.01), especially at the epicardialsite. BN and BN + Y blunted the ischemia-related shortening ofMAP90 and DSD, causing a reduction in repolarization timedispersion between the ischemic and normal zones. There were no significantchanges in the Vmax or DRD in the ischemic zone between periodsbefore and after an increase in each drug dose in the four groups. None ofthe seven dogs developed ventricular tachycardia (VT)/ventricularfibrillation (VF) in the Y group, whereas two of the eight dogs in theBN group, three of the nine dogs in the BN + Y group, and three ofthe nine dogs in the control group developed VT/VF. These results suggestthat the α1-adrenergic blocker bunazosin blunts theshortening effect of KATP channel activator on repolarizationtime, and that the KATP channel opener Y may be antiarrhythmic,although the repolarization time dispersion during myocardial ischemia isincreased. [ABSTRACT FROM AUTHOR]

Slug is a transcription factor involved in processes such as the formation of mesoderm and neural crest, two developmental events that imply a transition from an epithelial to a mesenchymal phenotype. During late cardiac morphogenesis, mesenchymal cells originate from two epithelia – epicardial mesothelium and cushion endocardium. We aimed to check if Slug is expressed in these systems of epithelial-mesenchymal transition. We have immunolocated the Slug protein in the heart of quail embryos between Hamburger and Hamilton stages HH16 and HH30. In the proepicardium (the epicardial primordium), Slug was detected in most cells, mesothelial as well as mesenchymal. Slug immunoreactivity was strong in the mesenchyme of the endocardial cushions and subepicardium from its inception until HH24, but the immunoreactivity disappeared in later embryos. Only a small portion of the endocardial cells located in the areas of epithelial-mesenchymal transition (atrioventricular groove and outflow tract) were immunolabelled, mainly between HH16 and HH20. Endocardial cells from other cardiac segments were always negative, except for a transient, weak immunoreactivity that coincided with the development of the intertrabecular sinusoids of the ventricle. In contrast, virtually all cells of the epicardial mesothelium were immunoreactive until stage HH24. The mesenchymal cells that migrate to the heart through the spina vestibuli were also conspicuously immunoreactive. The myocardium was not labelled in the stages studied. Our results stress the involvement of Slug in the epithelial to mesenchymal transition. We suggest that Slug can constitute a reliable marker of the cardiac epithelial cells that are competent to transform into mesenchyme as well as a transient marker of the epithelial-derived mesenchymal cells in the developing heart. [ABSTRACT FROM AUTHOR]

We investigated the response of refractory periods and blood flow to blockade of α1- and β-adrenoceptors alone, or in combination on endocardium and epicardium, during myocardial ischemia. Dogs were anesthetized with α-chloralose and divided into bunazosin (an α1-blocking agent)-treated (0.1–0.2 mg/kg, IV, n = 14), propranolol-treated (0.2 mg/kg, IV, n = 12), and vehicle-control (n = 10) groups. The diagonal branches of the left anterior descending artery were ligated. The refractory period (ERP) and blood flow (RMBF) were determined by an S1-S2 extrastimulus method and a nonradioactive microsphere technique, respectively. The duration of regional electrograms (DRE) was measured in the endocardial and epicardial sites. Bunazosin alone reversed the ischemia-related shortening of ERPs at both the endocardial and epicardial sites, with a greater effect seen epicardially (P < .05). Subsequent administration of propranolol further prolonged ERPs in both sites, although the effect was greater in the epicardial surface (P < .05). Bunazosin reduced RMBF to a greater degree at the endocardial site than at the epicardial site in the ischemic zone (P < .01 and P < .05, respectively), but the magnitude of the reduction in RMBF and the difference in RMBF between sites were similar to the control group (P < .01). Propranolol alone and subsequent administration of bunazosin prolonged the ERP more at the epicardial site (P < .01) than at the endocardial sites in the ischemic zone. Propranolol produced no significant difference in RMBF between both sites. DREs in animals treated with bunazosin and propranolol alone, or in combination, were similar to those in animals treated with vehicle. These results suggest that differences in ERPs between endocardium and epicardium with blockade of α1- and/or β-adrenoceptor are not due to concomitant alterations in RMBF, but to differences in electrophysiological properties of the endocardial and epicardial cells during the acute phase of myocardial ischemia. [ABSTRACT FROM AUTHOR]

The ultrastructure of the heart in Chimaera monstrosa L. is described. The endocardial and the epicardial cells are similar in the three cardiac regions. Myocardial cells show small variations. The myofibre, 4-6 μm thick, contains one or a few myofibrils. Each myosin filament is surrounded by six actin filaments. The sarcomere banding pattern includes the Z-, A-, I-, M-, N-, and H-band. End-to-end attachments between myofibres are composed of alternating desmosomes and fasciae adhaerentes. Desmosomes and nexuses occur between longitudinally oriented cell surfaces. The sarcoplasmic reticulum is poorly developed but well defined. Peripheral coupling-like structures are common, T-tubules are absent. Membrane bound dense bodies occur in all regions. Areas with ribosomes and single myosin filaments are often seen. The epicardial cells have a regular hexagonal surface and are much thicker than the endocardial cells. Numerous short and a few longer cytoplasmic extensions face the pericardial cavity. The fiat endocardial cells contain a large nucleus and small amounts of cytoplasm. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to determine the transmural adaptive changes that occur in cell size, myofibrils, and myosin isoforms from the endocardium (ENDO) to the epicardium (EPI) of the left ventricle (LV) of the rat heart during compensatory hypertrophy. Hypertrophy was induced by supra-renal aortic constriction for periods of 2, 7, 15 and 30 days. Percent left ventricular hypertrophy averaged 63±9.7% at 30 days following constriction. A significant (p <0.05) transmural gradient in the V myosin isoform (9±0.7% ENDO vs. 5±1.8% EPI) was initially observed at 7 days and was still evident by 30 days (25±3.6% ENDO vs 15±2.0% EPI). Cell cross-sectional area was also greater (p <0.05) in the ENDO than in the EPI at 7,15 and 30 days. MF diameter was determined only at 30 days and was found to be similar to control values in both the hypertrophied ENDO (sham 1.24±0.05 vs hyp 1.18±0.09 μm) and EPI (sham 1.17±0.08 vs hyp 1.06±0.08 μm). The combined effects of cardiac myocyte hypertrophy with no change in MF diameter resulted in a calculated increase of approximately 70% in the number of myofibrils per myocyte both in the ENDO and EPI. It was concluded that the adaptive strategy of the left ventricular free wall to pressure overload was to initially increase myocyte cross-sectional area and then switch myosin expression from V to V, both of which proceeds transmurally from the sub-endocardium towards the sub-epicardium. Along with these transmural adaptations, myofibrils increased in number while maintaining myofibrillar diameter with the apparent intent of conserving diffusion distance for calcium from the sarcoplasmic reticulum to the innermost contractile filaments of the myofibrils. [ABSTRACT FROM AUTHOR]

The rates of rest decay (for rest periods of between 0.5 min and 10 min) and recovery from the rested state (following 10 min of rest) of cell shortening and the amplitude of the intracellular calcium transient were compared in epicardial and endocardial ventricular myocytes isolated from rabbit hearts. The object of these experiments was to determine whether reported transmural differences in action potential duration, myosin type expression and metabolic enzyme content are able to influence the control of contraction. Cells isolated from these two regions of the ventricular wall displayed almost identical twitch shortening and calcium transient characteristics during steady-state electrical stimulation at 0.5 Hz. Despite this, rest decay of cell shortening was faster and recovery from the rested state slower in endocardial cells than in epicardial cells. Neither of these differences could be explained in terms of changes of calcium transient amplitude or time course. We tried to mimic the effect of prolonged rest by application of caffeine to empty the sarcoplasmic reticulum of calcium. The regional differences in recovery of contraction from the rested state were not reproduced in the recovery of contraction after caffeine application, suggesting that the effect is produced by something other than refilling of the sarcoplasmic reticulum. It is suggested that changes in factors that affect myofilament calcium sensitivity produce the regional differences in rest decay and post-rest recovery of contraction. [ABSTRACT FROM AUTHOR]

Experiments were performed on anaesthetized, open-chest dogs to determine the reflex effects on systemic blood pressure and heart rate produced by stimulation of the parietal pericardium with bradykinin and nicotine, and to compare these effects with those evoked by application of these substances to the visceral pericardium (epicardium) of the left ventricle. Bradykinin (0.01-6.0 μg) elicited reflex increases in blood pressure and heart rate when applied either to the parietal pericardium or to the ventricular epicardium; the responses evoked from both sites were dose-dependent from the threshold of 0.01 μg to a maximum at 1.0 μg of bradykinin. The reflex effects of bradykinin were not affected by either vagotomy or phrenic nerve section, but were suppressed by bilateral sectioning of the upper thoracic (T-T) white rami communicantes and stellectomy. In contrast to bradykinin, nicotine (20-100 μg) failed to produce any change in blood pressure and heart rate when applied to the parietal pericardium and evoked depressor responses when applied to the epicardium of the left ventricle; these depressor effects of nicotine were abolished by vagotomy. The results indicate that sympathetic, but not vagal, afferent endings innervating the parietal pericardium are susceptible to chemical stimulation. Bradykinin is a powerful algesic agent and is formed and released locally during inflammation. We suggest, therefore, that the pericardial sympathetic pressor reflex is nociceptive in nature and can be activated when kinin formation occurs during pericardial inflammation. [ABSTRACT FROM AUTHOR]

Epicardial mapping is an important method for locating the accurate portion of the accessory pathway. Mapping is usually executed by measuring the time of the major deflection (the activation time) between two electrodes about 1 mm apart. The epicardial isochrone map is made up of contour lines connecting points with an equal activation time on the epicardium. The paper describes a newly developed microcomputer-based system for drawing epicardial isochrone maps. In this system, a simplified algorithm is introduced to extract the excitation delay from intracardiac reference signals and epicardial activation signals. By applying the B-Spline function to drawing the excitation map, an excitation pattern which is similar to the original is, obtained for each standard excitation pattern. [ABSTRACT FROM AUTHOR]

Several techniques have been used to visualize the migration pattern of the epicardial cells from the proepicardial organ over the myocardial surface. As the epicardial cells contain keratin tonofilament bundles, we have incubated 92 whole-mount quail hearts with an anti-keratin antibody. This immunohistochemical method showed that the complete epicardial covering of the embryonic heart is preceded by the formation of three epicardial rings. The epicardial rings are formed on the outer myocardial surface in the grooves that separate the cardiac segments from each other. We have also documented timing and patterning of isolated epicardial islands. They are not encountered at random over the myocardial surface, but only along the edge of the advancing epicardial front border and in two defined future epicardial ring areas on the ventral side of the outflow tract. The epicardial islands suggest that in the quail free-floating parts of epicardium can attach to the myocardium. Characteristics of the surface of the myocardium at the transitional zones between the cardiac segments, as well as the three-dimensional remodelling of the heart during cardiac morphogenesis seem to play a role in the pattern in which the epicardium eventually completely ensheaths the myocardial surface. Congenital heart defects are often related to malpositioned transitional zones that dictate the pattern of epicardial outgrowth. As the embryonic position of the epicardial rings is mirrored in the pattern of the main arterial stems, the coronary vascularization pattern might be altered in congenitally malformed hearts as well. [ABSTRACT FROM AUTHOR]

In chick embryos, the formation of the epicardium proceeds from the attachment of a secondary sinuventricular mesocardium. This mesocardium is formed by the adhesion of pericardial villi with the dorsal surface of the heart. It was the aim of this study to clarify the role of the pericardial villi in the formation of the epicardium. For this purpose, the contact between the pericardial villi and the heart was prevented by placement of a piece of the shell membrane between them. After re-incubation, the hearts of the experimental embryos could be assigned to one of two different groups: hearts completely lacking a secondary mesocardium (Group A), and hearts without the sinu-ventricular but with a dystopic secondary mesocardium (Group B). In Group A, the formation of the epicardium and subepicardial mesenchyme was found to be severely disturbed. In Group B, the formation of the epicardium proceeded from the point of attachment of a dystopic secondary mesocardium; defective development of the subepicardial mesenchyme was not encountered. These results support the view that the epicardium is derived from the pericardial epithelium. [ABSTRACT FROM AUTHOR]

The development of the layer of connective tissue between ventricular epicardium and myocardium was studied during chick morphogenesis using electron microscopy, light microscopy and immunohistochemical techniques. This layer, called the subepicardium, increases rapidly in volume from embryonic day 6 to 11 (E6-E11) during mesenchymal cell invasion. Fibrous, matrix components are initially apparent at E11 to E16, and as fibrous connective tissue structures accumulate, subepicardial volume decreases. Antibody labeling shows that fibronectin is an early, prominent constituent of the subepicardium, and by E8, the subepicardium is the cardiac site most enriched in fibronectin. Collagen type III is present in circumferentially-oriented fibers at E8. During subsequent cardiac growth, collagen type III fibers become broadly distributed in the subepicardium, with some fibers appearing to attach myocardium to epicardium. Collagen type I fibers are not apparent until E10. At E12 collagen type I fibers are distributed circumferentially around the heart in bundles crimped into waves of low amplitude. Other collagen type I fibers are oriented radially in the subepicardium. During late cardiac morphogenesis and in fully-differentiated hearts, fibronectin and collagen types I and III are more concentrated in the subepicardium than within the myocardium. These observations suggest that the composition and organization of the subepicardial connective tissue may make important contributions to cardiac mechanics from the latter half of embryonic development through adulthood. [ABSTRACT FROM AUTHOR]

The formation of the epicardium was investigated in the mouse embryo using scanning electron microscopy (SEM) in order to establish a three-dimensional perspective concerning epicardial development in mammals. The epicardium first appears as aggregates of cells scattered on the caudal surface of the ventricle and atria where these regions face the septum transversum in a 9-day-old embryo. These aggregated cells seem to have originated from the mesothelial projections extending from the surface of the septum transversum. Then, the cells of each aggregate flatten, subsequently fusing with each other to form a continuous sheet of epicardium. The fusion of aggregates proceeds in a cranial direction. Finally, the bulbus cordis and truncus arteriosus become invested by migrating cells at the cranial end of the epicardial sheet about 11 days after fertilization. The present observations are discussed in comparison with those made previously in avian embryos. [ABSTRACT FROM AUTHOR]

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Body surface potential maps (BSPMs) recorded during pace mapping provide an important non-invasive means for identifying local cardiac events; recent clinical studies demonstrated that endocardial pacing sites can be resolved within less than 10 mm. We sought to determine whether similar spatial resolution could be achieved during epicardial pacing. Four patients who were undergoing either heart valve replacement (one), aortocoronary bypass graft (one), or both (two) were studied. In each patient, a pair of epicardial electrodes was placed intraoperatively at the middle aspect of the right ventricular free wall. The distance between the neighbouring electrodes was 10 mm. Five days after the surgery, ECGs were acquired from 35 leads during pacing from each epicardial electrode. We determined the distributions of QRS integrals (the net area under the ECG signal) and compared integrals corresponding to pacing from each of the adjacent electrodes using statistical indices. Student’s t-test was applied to these indices and in all the patients revealed that differences in distributions of QRS integral maps were statistically significant (p < 0.01). Results of our study indicate that the non-invasive acquisition of body surface ECGs could resolve epicardial breakthrough sites within 10 mm, which may be useful in facilitating therapeutic ablations in patients with ventricular tachycardias. [ABSTRACT FROM AUTHOR]