鸡胚心脏外形变化及心外膜的发生

本研究用扫描电镜、透射电镜和光镜,观察了早期鸡胚心脏发生的外形变化及心外膜的发生。1.心脏发生经历2个阶段,首先是心脏的成襻过程,心管表面的一定部位出现沟,沟相应部位内面出现嵴。心襻的完成,标志着心脏各部原基的确立。第2个阶段是心脏各部原基的进一步分化,包括心腔内部的分隔及心脏各部位置的变化。心房与心锥的移位,可能是受左右心室移位的影响。2.心外膜片并非由心肌外层原位分化,而是由静脉窦处的间充质细胞增殖,并迁移覆盖在心肌层表面形成。     

Model of cardiac arrest in rats established by modified transcutaneous electrical stimulation on epicardium北大核心CSCD

Objective To establish the cardiac arrest (CA) model in rats by modified transcutaneous elcctrical stimulation on epicardium. Methods This study was performed in the Emergency Medicine laboratory in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. After 10 Sprague-Dawley male rats weighing 330-380 g were anesthetized, two acupuncture needles connected to the anode and cathode of a stimulator were transcutaneously inserted into the epicardium as electrodes. The puncture points were located quantitatively according to the anatomical structure of the rat chest. The electrical stimulation was maintained for 3 minutes to induce ventricular fibrillation(VF). Cardiopulmonary resuscitation (CPR) included chest compressions, intravenous adrenaline and defibrillation operated at 6 min after a period of nonintervention. Results CA was induced after the implement of the effective electrical stimulation in all ten rats in this experiment. The average current intensity to induce VF was (1.80 ± 0.59) mA, the average time to induce CA was (5.07 ± 237) s, the average time of the total electrical stimulation was (187.50 ± 12.75) s and the total time of CA was 6 min. At the end of the electrical stimulation, 9 rats presented VF and 1 rat showed pulseless electrical activity. The restoration of spontaneous circulation was achieved in all 10 rats. The average time of CPR was(190.90±68.60) s, the mean numbers of defibrillation werc(1.20 ± 0.63), and he average number of adrenaline application were (1.20 ± 0.42) times. Neither visible hemorrhage on epicardium nor gross pulmonary congestion was observed. Conclusions The modified transcutaneous electrical stimulation on epicardium to produce CA model in rats is an easily applicable and effective technique. This model may provide an alternative for experimental research of CPR. © 2018 Chinese Medical Association. All rights reserved.     

Epicardium is required for sarcomeric maturation and cardiomyocyte growth in the ventricular compact layer mediated by transforming growth factor β and fibroblast growth factor before the onset of coronary circulation

The epicardium, which is derived from the proepicardial organ (PE) as the third epithelial layer of the developing heart, is crucial for ventricular morphogenesis. An epicardial deficiency leads to a thin compact layer for the developing ventricle; however, the mechanisms leading to the impaired development of the compact layer are not well understood. Using chick embryonic hearts, we produced epicardium‐deficient hearts by surgical ablation or blockade of the migration of PE and examined the mechanisms underlying a thin compact myocardium. Sarcomeric maturation (distance between Z‐lines) and cardiomyocyte growth (size) were affected in the thin compact myocardium of epicardium‐deficient ventricles, in which the amounts of phospho‐smad2 and phospho‐ERK as well as expression of transforming growth factor (TGF)β2 and fibroblast growth factor (FGF)2 were reduced. TGFβ and FGF were required for the maturation of sarcomeres and growth of cardiomyocytes in cultured ventricles. In ovo co‐transfection of dominant negative (dN)‐Alk5 (dN‐TGFβ receptor I) and dN‐FGF receptor 1 to ventricles caused a thin compact myocardium. Our results suggest that immature sarcomeres and small cardiomyocytes are the causative architectures of an epicardium‐deficient thin compact layer and also that epicardium‐dependent signaling mediated by TGFβ and FGF plays a role in the development of the ventricular compact layer before the onset of coronary circulation.     

注射用苦碟子对心肌缺血的影响

目的考察注射用苦碟子对实验性急性心肌缺血的保护作用及可能机制。方法采用结扎犬冠状动脉左前降支造成急性心肌缺血模型,测量心外膜心电图(E ECG)、心肌梗死面积、血清中乳酸脱氢酶(LDH)、磷酸肌酸肌酶(CK)、谷草转氨酶(GOT)、超氧化物歧化酶(SOD)的活力及丙二醛(MDA)含量。结果注射用苦碟子能显著降低心肌梗死犬的心肌梗死程度(ΣST)和心肌梗死范围(N ST)。注射用苦碟子2.4 g.kg-1可时间依赖性的降低冠脉结扎犬心肌梗死程度和心肌梗死范围,给药后30 minΣST即明显下降,ΣST在30 min和180 min分别较给药前降低了约29%和46%;N ST在60 min和180 min分别较给药前降低了约41%和46%;注射用苦碟子1.2、0.6 g.kg-1剂量组在120 min和180 min时,ΣST、N ST较90 min时略有上升,但与生理盐水对照组比较差异仍显著。注射用苦碟子可剂量依赖性的降低犬血清中LDH、GOT、CPK活力和MDA含量,升高SOD活力。结论注射用苦碟子对心肌缺血具有保护作用。     

Formation of the coronary vasculature during development

The formation of the coronary vasculature involves a series of carefully regulated temporal events that include vasculogenesis, angiogenesis, arteriogenesis and remodeling. This review explores these events, which begin with the migration of proepicardial cells to form the epicardium and end with postnatal growth and remodeling. Coronary endothelial, smooth muscle and fibroblast cells differentiate via epithelial–mesenchymal transformation; these cells delaminate from the epicardium. Following the formation of a tubular network by endothelial cells, an aortic ring of endothelial cells penetrates the aorta at the left and right aortic cusps to form the two ostia. Smooth muscle cell recruitment occurs rapidly and the coronary artery network begins forming as blood flow is established. Recent studies have identified a number of regulatory molecules that play key roles in epicardial formation and the transformation of its component cells into mesenchyme. Moreover, we are finally gaining some understanding regarding the interplay of angiogenic growth factors in the complex process of establishing the coronary vascular tree. Understanding coronary embryogenesis is important for interventions regarding adult cardiovascular diseases as well as those necessary to correct congenital defects.     

Chronic Amiodarone Reduces Transmural Dispersion of Repolarization in the Canine Heart

Amiodarone Reduces Transmural Dispersion. Introduction: Amiodarone is a potent antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias. In addition to its β-blocking properties, amiodarone is known lo block the sodium, potassium, and calcium channels in the heart. Its complex electropharmacology notwithstanding, the reasons for the high efficacy of the drug remain unclear. Also not well understood is the basis for the low incidence of proarrhythmia seen with amiodarone relative to other agents with Class III actions. The present study was designed to examine the effects of chronic amiodarone in epicardial, endocardial, and M cells of the canine left ventricle. Methods and Results: We used standard microelectrode techniques to record transmembrane activity from endocardial, epicardial, mid-myocardial, and transmural strips isolated from the canine left ventricle. Tissues were obtained from mongrel dogs receiving amiodarone orally (30 to 40 mg/kg per day) for 30 to 45 days or from untreated controls. Chronic amiodarone produced a greater prolongation of action potential duration in epicardium and endwardium, but less of an increase, or even a decrease at slow rates, in the M region, thereby reducing transmural dispersion of repolarization. In addition, chronic amiodarone therapy suppressed the ability of the I_kr, blocker, d-sotalol, to induce a marked dispersion of repolarization or early afterdepolarization activity. Conclusion: Our data demonstrate for the first time a direct effect of chronic amiodarone treatment to differentially alter the cellular electrophysiology of ventricular myocardium so as to produce an important decrease in transmural dispersion of repolarization, especially under conditions in which dispersion is exaggerated. These results may contribute to our understanding of the effectiveness of amiodarone in the treatment of life-threatening arrhythmias as well as to our understanding of the low incidence of proarrhythmia attending therapy with chronic amiodarone in comparison with other Class III agents.     

Coronary vessel development and insight towards neovascular therapy

Formation of the coronary arteries consists of a precisely orchestrated series of morphogenetic and molecular events which can be divided into three distinct processes: vasculogenesis, angiogenesis and arteriogenesis ( Risau 1997 ; Carmeliet 2000 ). Even subtle perturbations in this process may lead to congenital coronary artery anomalies, as occur in 0.2–1.2% of the general population ( von Kodolitsch et al. 2004 ). Contrary to the previously held dogma, the process of vasculogenesis is not limited to prenatal development. Both vasculogenesis and angiogenesis are now known to actively occur within the adult heart. When the need for regeneration arises, for example in the setting of coronary artery disease, a reactivation of embryonic processes ensues, redeploying many of the same molecular regulators. Thus, an understanding of the mechanisms of embryonic coronary vasculogenesis and angiogenesis may prove invaluable in developing novel strategies for cardiovascular regeneration and therapeutic coronary angiogenesis.     

PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts

A zebrafish heart can fully regenerate after amputation of up to 20% of its ventricle. During this process, newly formed coronary blood vessels revascularize the regenerating tissue. The formation of coronary blood vessels during zebrafish heart regeneration likely recapitulates embryonic coronary vessel development, which involves the activation and proliferation of the epicardium, followed by an epithelial-to-mesenchymal transition. The molecular and cellular mechanisms underlying these processes are not well understood. We examined the role of PDGF signaling in explant-derived primary cultured epicardial cells in vitro and in regenerating zebrafish hearts in vivo. We observed that mural and mesenchymal cell markers, including pdgfrβ, are up-regulated in the regenerating hearts. Using a primary culture of epicardial cells derived from heart explants, we found that PDGF signaling is essential for epicardial cell proliferation. PDGF also induces stress fibers and loss of cell-cell contacts of epicardial cells in explant culture. This effect is mediated by Rho-associated protein kinase. Inhibition of PDGF signaling in vivo impairs epicardial cell proliferation, expression of mesenchymal and mural cell markers, and coronary blood vessel formation. Our data suggest that PDGF signaling plays important roles in epicardial function and coronary vessel formation during heart regeneration in zebrafish.     

Improved Spatial Resolution for Cardiac Mapping Using Current Source Density-Based Electrode Arrays

The time of the minimum slope (i.e., the fastest negative deflection) in monopolar (MP) electrograms from normal hearts compares closely with time of phase 0 of the action potential in cells underlying the electrode, but poor rejection of far-field activity may limit the utility ofMP electrode technology in dense arrays used for the study of ventricular tachycardia and fibrillation. The purpose of this study is to evaluate more myopic discrete bipolar (BP) and nondirectional, two-dimensional current source density (CSD) based arrays for rejection of far-field potentials and precision of activation time determination. Simultaneous recordings of the CSD, MP, and multiple BP electrograms were performed on normal dog epicardium. The time of the minimum slope in MP electrograms was compared to activation times in CSD and BP derivations using: (1) peak; (2) steepest slope; (3) zero crossing of the steepest sloping segment in either direction; and (4) waveform morphology. In vivo, CSD amplitude was reduced significantly more than MP and BP amplitudes by insertion of inert media between the heart and the electrodes. The time of the steepest slope in CSD electrograms designated activation times closest to the time of the minimum slope in MP electrograms (0.9 ± 1.3 msec). We conclude that CSD provides a nondirectional electrode system that accurately defines the time of local activation and possesses better spatial specificity than MP electrode systems and BP electrode systems having the same interelectrode distances.