Myocardial Morphological Characteristics and Proarrhythmic Substrate in the Rat Model of Heart Failure Due to Chronic Volume Overload

Chronic volume overload leads to cardiac hypertrophy and later to heart failure (HF), which are both associated with increased risk of cardiac arrhythmias. The goal of this study was to describe changes in myocardial morphology and to characterize arrhythmogenic substrate in rat model of developing HF due to volume overload. An arteriovenous fistula (AVF) was created in male Wistar rats between the inferior vena cava and abdominal aorta using needle technique. Myocardial morphology, tissue fibrosis, and connexin43 distribution, localization and phosphorylation were examined using confocal microscopy and Western blotting in the stage of compensated hypertrophy (11 weeks), and decompensated HF (21 weeks). Heart to body weight (BW) ratio was 89% and 133% higher in AVF rats at 11 and 21 weeks, respectively. At 21 weeks but not 11 weeks, AVF rats had pulmonary congestion (increased lung to BW ratio) indicating presence of decompensated HF. The myocytes in left ventricular midmyocardium were significantly thicker (+8% and +45%) and longer (+88% and +97%). Despite extensive hypertrophy, there was no excessive fibrosis in the AVF ventricles. Distribution and localization of connexin43 were similar between groups, but its phosphorylation was significantly lower in AVF hearts at 21st week, but not 11th week, suggesting that HF, rather than hypertrophy contributes to the connexin43 hypophosphorylation. In conclusion, volume overload leads to extensive eccentric hypertrophy, but not to myocardial fibrosis. Increased vulnerability to arrhythmia in this HF model is possibly related to gap junction remodeling with hypophosphorylation of connexin43. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

慢性心衰时心肌细胞的形态学特点

为探讨升主动脉缩窄慢性心衰大鼠左、右心室心肌细胞形态学特点 ,利用游离心肌细胞技术 ,对心衰大鼠左、右心室心肌细胞进行常规 HE染色及电镜 ( TEM,SEM)观察。结果发现心衰时左、右心室心肌细胞的长度、宽度及面积都显著增加 ;右心室心肌细胞成比例肥大 ,心肌细胞超微结构改变不显著 ,而左心室心肌细胞超微结构改变明显。在心衰组及对照组左心室心肌中有两条毛细血管压迹的细胞。本研究分析了上述改变与心衰间的关系     

Development of the Juxta‐Oral Organ in Rat Embryo

The aim of this work is to clarify the development and morphology of the juxta‐oral organ (JOO) in rat embryos from Day (E)14 to 19. Furthermore, in the region of the JOO, an analysis was made of the expression of the monoclonal antibody HNK‐1, which recognizes cranial neural‐crest cells. In this study, we report that JOO develops from an epithelial condensation at the end of the transverse groove of the primitive mouth at E14. During E15, it invaginates and is disconnected from the oral epithelium. At E16, the JOO forms an solid epithelial cord with three parts (anterior, middle, and posterior) and is related to the masseter, temporal, medial pterygoid, and tensor veli palatini muscles. During E17‐19, no significant changes were detected in their position. Both the mesenchyme caudal to the anlage of the JOO at E14, as well as the mesenchyme that surrounds the bud of the JOO at E15, expressed positivity for HNK‐1. Our results suggest that the mesenchyme surrounding the JOO at E15 could emit some inductive signal for the JOO to reach its position at E16. This work shows for the first time that the cranial neural‐crest‐derived mesenchyme participates in the development of the JOO. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

大鼠和小鼠胚胎后肾移植的形态学研究

目的观察不同胚龄的大鼠和小鼠的后肾植入同种异体远交系成年宿主体内后的生长变化,探讨胚胎后肾移植的最佳胚龄及血管起源。方法应用光、电镜及免疫组织化学技术观察不同胚龄的后肾移植后,肾脏各部的发育情况及后肾内CD31+阳性细胞的分布。结果离体后肾移植10天后成熟的肾小体形成,胚龄16天的大鼠和胚龄13天的小鼠后肾移植10天后,排斥反应轻微;胚龄20天的大鼠后肾和胚龄14、16天的小鼠后肾移植10天后,出现明显排斥反应,且随着胚龄的增长排斥反应逐渐加重。CD31+阳性细胞分布在肾小体毛细血管内皮及部分皮质中的间质细胞。结论胚龄16天的大鼠和胚龄13天的小鼠后肾中均无成熟肾小体出现,是移植的最佳时间;后肾移植物内的毛细血管袢是由移植物的间质细胞分化而来的。     

Contractile and Electrical Functions of Rat Heart during Left Ventricular Hypertrophy

Left ventricular hypertrophy of the hearts in Wistar rats caused by renovascular hypertension prolongs depolarization of epicardial surface of the ventricles and increases the duration of excitation phase in the left ventricular epicardium. Sex-related differences in changes of myocardial contractility were revealed during hypertrophy of the left ventricle caused by renovascular hypertension.     

Development of the stapes and associated structures in human embryos

The objective of this study was to clarify the development of the stapes in humans and its relationship with the cartilage of the second branchial arch. The study was carried out in 25 human embryos between 6 and 28 mm crown-rump length. The stapes develops at the cranial end of the second branchial arch through an independent anlage of the cartilage of this arch. Between the stapedial anlage and the cranial end of the Reichert's cartilage there is a formation called the interhyale, the internal segment of which gives rise to the tendon of the stapedial muscle. The stapedial anlage is a unique formation with two distinct parts: the superior part that will comprise the base and the inferior part that will be crossed by the stapedial artery during embryonic development and will constitute the limbs and the head of the stapes. According to the results, the otic capsule is not involved in formation of the base of the stapes.     

Initial stages of development of the submandibular gland (human embryos at 5.5–8 weeks of development)

The aim of this study was to determine the main stages of submandibular salivary gland development during the embryonic period in humans. In addition, we studied submandibular salivary gland development in rats on embryonic days 14–16 and expression in the submandibular salivary gland region with the monoclonal antibody HNK‐1. Serial sections from 25 human embryos with a greatest length ranging from 10 to 31 mm (Carnegie stages 16–23; weeks 5.5–8 of development) and Wistar rats of embryonic days (E) 14–16 were analysed with light microscopy. Five stages of submandibular salivary gland development were identified. The prospective stage (1), between weeks 5.5 and early week 6, is characterized by a thickening of the epithelium of the medial paralingual groove in the floor of the mouth corresponding to the primordium of the submandibular salivary gland parenchyma. At this stage, the primordium of the parasympathetic ganglion lies below the lingual nerve. The primordium of the submandibular salivary gland parenchyma is observed in rats on E14 in the medial paralingual groove with mesenchymal cells, underlying the lingual nerve. These cells are HNK‐1‐positive, corresponding to the primordium of the parasympathetic ganglion. The bud stage (2), at the end of week 6 in humans and on E15 in rats, is characterized by the proliferation and invagination of the epithelial condensation, surrounded by an important condensation of the mesenchyme. The pseudoglandular stage (3) at week 6.5 is characterized by the beginning of the formation of lobes in the condensed mesenchyme. The canalicular stage (4), between week 7 and 7.5, is characterized by the appearance of a lumen in the proximal part of the submandibular duct. The innervation stage (5) occurs during week 8, with the innervation of the submandibular and interlobular ducts. Nervous branches arriving from the parasympathetic ganglion innervate the glandular parenchyma. Numerous blood vessels are observed nearby. Our results suggest that submandibular salivary gland development requires interactions among epithelium, mesenchyme, parasympathetic ganglion and blood vessels.     

Preclinical Study of the Effect of Cardiotropic Agents on Isolated Heart

Direct effects of cardiotropic preparations on the hearts isolated from Wistar rats were examined. Deenergization of cardiomyocytes was modeled under conditions of hypoxic perfusion. Recovery of cardiac function during reperfusion was assessed by changes in the heart rate and contraction amplitude.     

Mitochondrial Division in Rat Cardiomyocytes: An Electron Microscope Study

In cardiomyocytes of rats, two distinct mitochondrial division processes are in operation. The predominant process involves extension of a single crista until it spans the full width of a mitochondrion. Ingrowth of the outer membrane ultimately results in scission. The second division process involves “pinching,” in which narrowing of the organelle at specific surface locations leads to its attenuation. When limiting membranes from opposite sides meet, mitochondrial fission ensues. When pinching is the operative mode, elements of sarcoplasmic reticulum always are associated with the membrane constrictions. The nuclear control mechanisms that determine which modality of mitochondrial division will prevail are unknown. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

T-box基因与脊椎动物心脏发育

T-box基因家族在脊椎动物心脏发育中起重要作用,主要作用于脊椎动物的早期心脏谱系决定、心室特化、房室分隔和胚胎传导系统分化等。该基因家族主要包括Tbx1、Tbx2、Tbx3、Tbx5、Tbx18和Tbx20。这些基因在心脏发育过程中表现出复杂的时间、空间调节作用。本文从分子水平上对T-box基因在心脏的发生发展过程中所起的作用作一综述。     

Morphogenesis of the human lacrimal gland

The aim of this study was to determine the main stages of the lacrimal gland's developmental process in humans and to establish its precise morphogenetic timetable. Its onset is generally assumed to take place at O'Rahilly's stage 21, arising from an epithelial thickening of the superior extreme of the temporary conjunctival fornix. However, the present study points to a prior stage in the process: the presence of epithelial-mesenchymal changes in embryos at O'Rahilly's stage 19. The study was performed using light microscopy on serial sections of 37 human specimens: 23 embryos and 14 fetuses ranging from 15 to 137 mm crown-rump length (7-116 weeks of development). Three stages in lacrimal gland morphogenesis were identified: (1) the presumptive glandular stage, O'Rahilly's stages 19-20, characterized by a thickening of the superior fornix epithelium together with surrounding mesenchymal condensation; (2) the bud stage, generally assumed to be the first manifestation of glandular origin, characterized initially by the appearance of nodular formations in the region of the superior conjunctival fornix and concluding with the appearance of lumina within the epithelial buds; and (3) the glandular maturity stage, weeks 9-16, the period in which the gland begins to take on the morphology of adulthood.     

Morphogenesis of the human excretory lacrimal system

The aim of this study was to determine the principal developmental stages in the formation of the excretory lacrimal system in humans and to establish its morphogenetic period. The study was performed using light microscopy on serial sections of 51 human specimens: 33 embryos and 18 fetuses ranging from 8 to 137 mm crown-rump length (CR; 5-16 weeks of development). Three stages were identified in the morphogenesis of the excretory lacrimal system: (1) the formative stage of the lacrimal lamina (Carnegie stages 16-18); (2) the formative stage of the lacrimal cord (Carnegie stages 19-23); and (3) the maturative stage of the excretory lacrimal system, from the 9th week of development onward. A three-dimensional reconstruction of the excretory lacrimal system was performed from serial sections of an embryo at the end of the embryonic period (27 mm CR).     

Remodeling of the Embryonic Interventricular Communication in Regard to the Description and Classification of Ventricular Septal Defects

Ventricular septal defects are the commonest congenital cardiac malformations. Appropriate knowledge of the steps involved in completion of ventricular septation should provide clues as to the morphology of the different phenotypes. Currently, however, consensus is lacking regarding the components of the developing ventricular septum, and how best to describe the different phenotypes seen in postnatal life. We have reassessed the previous investigations devoted to closure of the embryonic interventricular communication. On this basis, we discuss how studies in the early part of the 20th century correctly identified the steps involved in the remodeling of the embryonic interventricular foramen subsequent to the stage at which the outflow tract arises entirely above the cavity of the developing right ventricle. There has, however, already been remodeling of the foramen from the stage at which the atrioventricular canal is supported exclusively by the developing left ventricle. We show how these temporal changes in morphology can provide explanations for the different ventricular septal defects seen in the clinical setting. Thus, muscular defects represent inappropriate coalescence of muscular ventricular septum. The channels that are perimembranous are due to failure of closure of the persisting embryonic interventricular foramen. Those that are doubly committed and juxta-arterial reflect failure of formation of the free-standing subpulmonary muscular infundibular sleeve. The findings also point to the importance of appropriate alignment, during development, between the developing atrial and ventricular septums, and between the apical component of the ventricular septum and the ventricular outlet components. Anat Rec, 302:19–31, 2019. © 2018 Wiley Periodicals, Inc.     

Optical Coherence Tomography as a Tool for Measuring Morphogenetic Deformation of the Looping Heart

Optical coherence tomography (OCT) was used to investigate morphogenesis of the embryonic chick heart during the first phase of looping (c‐looping), as the heart bends and twists into a c‐shaped tube. The present study focuses on the morphomechanical effects of the splanchnopleure (SPL), a membrane that has been shown to play a major role in cardiac torsion by pressing against the ventral surface of the heart. Without the SPL, rightward torsion (rotation) is delayed. The images show that compressive forces exerted by the SPL alter the shapes of the heart tube and primitive atria, as well as their spatial relationships. The SPL normally holds the heart in the plane of the embryo and forces cardiac jelly (CJ) out of adjacent regions in the atria. When the SPL is removed, cross‐sections become more circular, CJ is more uniformly distributed, and the heart displaces ventrally. In addition, OCT‐based morphogenetic strain maps were measured during looping by tracking the three‐dimensional motions of microspheres placed on the myocardium. The spatial–temporal patterns of the strains correlated well with the observed behavior of the heart, including delayed torsion that occurs in SPL‐lacking embryos. These results illustrate the potential of OCT as a tool in studies of morphogenesis, as well as provide a better understanding of the mechanical forces that drive cardiac looping. Anat Rec, 290:1057–1068, 2007. © 2007 Wiley‐Liss, Inc.     

Impact of Intrauterine Growth Restriction on the Capillarization of the Early Postnatal Rat Heart

Capillarization plays a key role in the growth of the developing heart. We therefore hypothesized that impaired heart development following intrauterine growth restriction (IUGR) may arise from inadequate myocardial capillary growth. The aims of the study were to examine the effect of IUGR on the growth and diffusion radius of intramyocardial capillaries in rats at postnatal day 1. Uteroplacental insufficiency was induced in rats in late gestation (E18, term = E22) by bilateral uterine artery and vein ligation (restricted offspring N = 12; six males and six females); offspring from sham-operated dams were used as controls (N = 10; five males and five females). At postnatal day 1, the hearts were immersion-fixed and heart volume, capillary length density, capillary diffusion radius, and total capillary length were stereologically determined. Restricted offspring were significantly smaller at birth, with a concomitant reduction in heart volume and total myocardial capillary length compared to controls. Capillary growth was not impaired relative to heart size, with no significant differences in capillary length density or diffusion radius in the myocardium of restricted and control offspring. There were no sex differences in any of the parameters examined. In conclusion, there was no evidence to indicate that microvascular development is compromised in the heart of IUGR offspring at 1 day after birth. Total myocardial capillary length, however, was significantly reduced in the growth restricted offspring and further longitudinal studies are required to elucidate the long-term impact, particularly following hypertrophic cardiac growth. Anat Rec, 302:1580–1586, 2019. © 2018 American Association for Anatomy     

小鼠耳蜗发育的形态学研究

目的：探讨小鼠耳蜗发育的特点及规律。方法：应用光镜对昆明种小白鼠耳蜗从胚胎第１０天至出生后第１４天的整个发育过程进行形态学研究。结果：小鼠耳蜗的整个形态发育过程可分为三个时期：⑴听泡发育期;⑵蜗管上皮增殖期;⑶耳蜗各部分结构的分化结构的分化期和发育成熟期。结论：小鼠在出生时,其耳蜗膜迷路的大部分结构成份已经形成,出生后则需进一步的分化发育,至出生后２周时才完全发育成熟。小鼠耳蜗管上皮的分化是从底周