Innervation of pulmonary veins: Morphologic pattern and pathways of nerves in the human fetus

The aim of the study was to determine the anatomy of intrinsic nerves supplying human pulmonary veins (PVs). Twenty-two hearts of human fetuses with full sets of PVs were examined using a histochemical method for acetylcholinesterase in order to stain transmurally intrinsic neural structures on non-sectioned PVs for subsequent stereomicroscopic examination. Findings of the study demonstrate that epicardiac nerve extensions from both the dorsal right atrial and the middle dorsal subplexuses reached the right superior as well as the right inferior PVs, whereas the left superior PV was supplied by nerve extensions from the left dorsal subplexus. The left and middle dorsal subplexuses contributed nerves to the left inferior PV. The ganglia related topographically to PVs were patchy in distribution. On the left and right superior PVs, 38±6 and 31±3 ganglia were found, respectively, whereas 46±7 and 38±7 ganglia were identified on the left and right inferior PVs. The size of ganglia was similar for all four veins, ranging in area from 0.004±0.0003 to 0.007±0.0004 mm². The total area of ganglia distributed on a given PV was similar, ranging from 0.15±0.0003 to 0.25±0.0004 mm². The present findings demonstrate that the richest ganglion sites supplying intrinsic nerves to the human PVs are located on the posterior sides of both inferior and the left superior PVs and, therefore, these sites may be considered primary targets for focal pulmonary vein ablation in catheter-based therapy of atrial fibrillation.     

The mandibular body of the human fetus. Histologic analysis of the basilar part

Summary Histologic and microradiographic analyses of 47 human mandibles from 42 fetuses and 5 neonates have been carried out to study the development of the mandibular body. This not only entails woven bone formation along Meckel's eartilage but also endochondral ossification in the condylar cartilage, the pillars of which are included in the posterior part of the mandibular body. Progressively, woven bone is replaced by lamellar bone, and typical Haversian system are already present at the fifth month of fetal life. This early occurrence of bone remodelling is related to the fact that the mandible is subjected to intense activity from sucking and swallowing.This study has been supported by a grant of the Fonds de la Recherche Scientifique Médicale (F.R.S.M., Brussels, Belgium)     

The volume of the carotid body and periadventitial type I and type II cells in the carotid bifurcation region of the fetal cat and kitten

Summary The bilateral distribution of carotid body type I cells was investigated in 6 fetuses (gestational age 95%) and 9 newborn kittens (aged 1 day to 4 days) by serially sectioning the carotid bifurcation regions. In most specimens type I cells occurred in close proximity to the wall of the occipital artery or one of its small proximal branches within a division of connective tissue with defineable but irregular borders. This combination of type I cells and connective tissue constituted the principal mass of the carotid body. Using an interacting image analysis system, the area of the carotid body in each serial section was measured by accurately contouring its perimeter. The volume of the carotid body was calculated by multiplying the sum of the areas of the serial sections by the thickness of the section. The volume of the carotid body was 0.052±0.018 mm³ in the fetuses and 0.025–0.117 mm³ in the 1–4 day old kittens. A degree of symmetry in the values for the volume of the right and left carotid body was found. Caudally, and separate from the principal mass of carotid body type I cells, isolated groups of periadventitial type I cells were noted in the connective tissues around the occipito-ascending pharyngeal trunk, origin of the occipital artery and rostral end of the common carotid artery in 7 out of 12 specimens from fetal cats and 11 out of 18 specimens in newborn kittens. The volumes of the periadventitial groups of cells ranged between 25–1,365 m³ in fetuses and 10–1,351 m³ in kittens.     

The carotid body and arousal in the fetus and neonate

Arousal from sleep is a major defense mechanism in infants against hypoxia and/or hypercapnia. Arousal failure may be an important contributor to SIDS. Areas of the brainstem that have been found to be abnormal in a majority of SIDS infants are involved in the arousal process. Arousal is sleep state dependent, being depressed during AS in most mammals, but depressed during QS in human infants. Repeated exposure to hypoxia causes a progressive blunting of arousal that may involve medullary raphe GABAergic mechanisms. Whereas CB chemoreceptors contribute heavily to arousal in response to hypoxia, serotonergic central chemoreceptors have been implicated in the arousal response to CO₂. Pulmonary or chest wall mechanoreceptors also contribute to arousal in proportion to the ventilatory response and decreases in their input may contribute to depressed arousal during AS. Little is known about specific arousal pathways beyond the NTS. Whether CB chemoreceptor stimulation directly stimulates arousal centers or whether this is done indirectly through respiratory networks remains unknown. This review will focus on arousal in response to hypoxia and CO₂ in the fetus and newborn and will outline what we know (and do not know) about the involvement of the carotid body in this process.     

Histological changes associated with ageing of the human carotid body

A qualitative and quantitative histological study was made of the carotid bodies obtained at necropsy from 47 subjects ranging in age from 14 to 100 years. With increasing age there is a loss of more than a third of the amount of glomic tissue with a diminution in the size of the lobules. In young people the basic histological pattern of clusters, composed of cores of chief cells with surrounding rims of sustentacular cells, has commonly superimposed on it prominence of the dark variant of chief cells. In middle-aged subjects there is proliferation of sustentacular cells which appear to merge imperceptibly into fibrosis of the lobules and becomes associated with diffuse or focal infiltrates of lymphocytes.     

Location and variability of epicardiac ganglia in human fetuses

The aim of the study was to determine the morphology of epicardiac ganglia in human fetuses at different stages of their development as these ganglia are considered to be of a pivotal clinical importance. Twenty-one fetal hearts were investigated applying a technique of histochemistry for acetylcholinesterase to visualize the epicardiac neural ganglionated plexus with its subsequent stereoscopic examination on total organs. In all of the examined fetuses, epicardiac neural plexus with numerous ganglia was well recognizable and could be clearly differentiated into seven ganglionated subplexuses, topography and structural organization of which were typical for hearts of adult human. The largest ganglion number comprising 77% of all counted ganglia was identified on the dorsal atrial surface. Fetal epicardiac plexus in gestation period of 15–40 weeks contained 929 ± 62 ganglia, but ganglion amount did vary substantially from heart to heart. In conclusion, this study implies that the human fetal epicardiac ganglia occupy their definitive location already at gestation period from 15 weeks and their number as well as distribution on heart surface presumably is not age dependent.     

The influence of chronically hypoxemic states on human carotid body structure and cardiac hypertrophy

Summary Quantitative and qualitative changes in the human carotid body morphology, and their relationship to changes in the weight of right and left ventricles were investigated in 10 patients with a history of chronic hypoxemia. 5 patients without a history of cardiac, pulmonary or cerebral respiratory failure served as the control group. In the chronically hypoxemic group, a 2.67-fold increase in the total specific glomus cell volume was found. Up to a critical volume this increase is due to hypertrophy, beyond that it is due to hyperplasia. The course of the morphologic changes under the influence of slowly progressive chronic hypoxemia is discussed in a frame work of three stages (stage I = hypertrophy, stage II = nodular hyperplasia, stage III = atrophy). Plasmacellular infiltrates are constant though sometimes sparse. They are mostly perineural in location, less often intralobular and if so almost exclusively periglomoidal. In one case, we found an increase of Schwann cells in the interstitial and periglomoidal space without demonstrable degeneration of the nerve fibres themselves. Our hypothesis suggests that degeneration of special nerve terminals of the reciprocal type occurs in afferent nerve fibers. The increase of right ventricular weight (by a factor of 2.05) is significant, in contrast to that of the left. A linear correlation between the increase of right ventricular weight and the increased total glomus cell volume was not established. In 4 cases, however, we found pulmonary hypertensive vascular changes, which might be responsible for the disparity in the linear relationship.Dedicated to Prof. Dr. J.R. Rüttner on the occasion of his 60th birthday     

Structural and neurochemical changes in the maturation of the carotid body

Functional maturation of the carotid body in the postnatal period relies partly on structural and neurochemical changes, which are reviewed here. Structural changes include changes in cytological composition, and increases in glomic tissue volume, dense-cored granules of type I cells, synapses of type I cells with type II cells and afferent nerve fibres. Vascular volume also increases, but in the same proportion as extravascular volume. During maturation, the carotid body also shows higher density and hypoxic sensitivity of K⁺-channels and an increased hypoxic [Ca²⁺]_i response. Modulation of content and release of catecholamine occurs, together with decreased expression of tyrosine hydroxylase and dopamine β-hydroxylase and increased expression of choline acetyltransferase. Expression of dopamine 2 receptor and nicotinic α3 and α7 receptor subunits increases, and muscarinic M1 receptor protein, nicotinic α4 and β2 receptor subunits and adenosine receptor 1 decrease. Maturation of the carotid body may also be explained with reference to the developmentally regulated expression of trophic factors and their receptors.     

The carotid body in Sudden Infant Death Syndrome

The aim of the present study is to provide a review of cytochemical, clinical and experimental data indicating disruption of perinatal carotid body maturation as one of the possible mechanisms underlying SIDS pathogenesis. SIDS victims have been reported to show alterations in respiratory regulation which may partly be ascribed to peripheral arterial chemoreceptors. Carotid body findings in SIDS victims, although not entirely confirmed by other authors, have included reductions in glomic tissue volume and cytoplamic granules of type I cells, changes in cytological composition (higher percentages of progenitor and type II cells) and increases in dopamine and noradrenaline contents. Prematurity and environmental factors, such as exposure to tobacco smoke, substances of abuse, hyperoxia and continuous or intermittent hypoxia, increase the risk of SIDS and are known to affect carotid body functional and structural maturation adversely, supporting a role for peripheral arterial chemoreceptors in SIDS.     

Comparative embryology of the carotid body

Vertebrate carotid bodies and related structures (branchial arch oxygen chemoreceptors in fishes, carotid labyrinth in amphibians, chemoreceptors in the wall of the common carotid and its branches in birds) develop in embryos when neural crest cells, blood vessels, and nerve fibers from sympathetic and cranial nerve ganglia invade mesenchymal primordia in the wall of the 3rd branchial arch. This review focuses on literature published since the 1970s investigating similarities and differences in the embryological development of 3rd arch oxygen chemoreceptors, especially between mammals and birds, but also considering reptiles, amphibians and fishes.     

The carotid body of the harbour seal (Phoca vitulina richardsi)

Summary The bilateral distribution of carotid body type 1 and 11 cells was investigated in five harbour seals (Phoca vitulina richardsi), by serially sectioning the carotid bifurcation regions. The cells occurred bilaterally in the animals and were also present in one specimen from a sixth animal available for study. The type 1 and 11 cells were located in the space between the internal and external carotid arteries and had a varied relationship to the occipital and condyloid arteries. They lay within a division of connective tissue with irregular but defineable borders and this combination of connective tissue and type 1 and 11 cells constituted the principal mass of the carotid body. The carotid body occurred in a variety of forms: wedge-shaped, crescentic or horse-shoe shaped, or as a discrete oval structure. In some specimens the carotid body had a central neurovascular core of small blood vesels and nerves. The artery to the organ originated from either the external carotid, internal carotid or common carotid arteries. Using an interactive image analysis system in eight specimens, which had been perfusion-fixed at a normal arterial pressure, the mean volume of the carotid body was 1.666±0.45 (SD) mm³. Caudally and separate from the principal mass of the carotid body periadyentitial type 1 and 11 cells were noted in 4 out of 11 specimens in the connective tissues adjacent to the external carotid artery, origin of the occipital, and the rostral part of the common carotid artery and its bifurcation.     

国人胚胎顶骨组织结构的胎龄性变化

目的　完善国人胚胎颅顶骨发生及发育的形态学资料。方法　取第 9～ 38周人胚胎 32例的颅顶骨 ,用HE、硫堇 苦味酸法染色 ,光镜观察。结果　第 9周胚胎顶骨为一片间充质膜。第 10～ 12周胚胎的膜性顶骨内 ,血管丰富 ,有针片状骨小梁形成 ;第 13～ 16周胚胎顶骨内骨小梁增加 ,呈条索状。第 17周以后 ,顶骨内的骨小梁增粗增长 ,连接成骨小梁网 ,并有原始哈氏系统形成 ;第 2 9周以后 ,顶骨内的原始哈氏系统不断增加 ,原始密质骨逐渐形成。结论　人胚胎颅顶骨发育过程中有原始哈氏系统形成 ,胚胎颅骨的发育及结构特点与胚胎脑的不断生长 ,使其承受的重量不断增加有关     

Distribution of carotid body type I cells and other periadventitial type I cells in the carotid bifurcation regions of the cat

Summary The bilateral distribution of carotid body type I cells was investigated in five non-pedigree cats by serially sectioning the carotid bifurcation regions. Carotid body type I cells occurred bilaterally in close proximity to the wall of the occipital artery or one of its proximal branches, and less frequently the ascending pharyngeal artery within a division of connective tissue with defineable but irregular borders. Caudally, and separate from the principal mass of carotid body type I cells, isolated groups of periadventitial type I cells were found in seven out of ten specimens lying freely in the connective tissues around the occipito-ascending pharyngeal trunk and the origin of the occipital artery immediately rostral to the carotid bifurcation. Periadventitial type I cells were not observed at the level of the carotid bifurcation but on one occasion these cells were noted caudal to the carotid bifurcation lying adjacent to the wall of the rostral end of the common carotid artery. From our data on four specimens, reconstructions were made of the carotid body. The occurrence and significance of the periadventitial type I cells is discussed.     

Monoamines and their catabolites in the rabbit carotid body

Monoamines and their metabolites have been measured by high performance liquid chromatography with electrochemical detection, in control rabbit carotid bodies and under several experimental conditions: 1) at different times (3 h, 6 h, 24 h, 48 h) after intravenous injection of reserpine (5 mg/kg); 2) 14 days after sympathectomy; 3) 14 days after section of the carotid sinus nerve. The results were analyzed with probability plotting methods. Dopamine was the most important monoamine in the carotid body (CB) and its variations were very large. It was almost entirely depleted by reserpinization without simultaneous increase in 3,4-dihydroxyphenylacetic acid. Sympathectomy increased dopamine content but did not change noradrenaline content. However data analysis suggested that noradrenaline might be compartmented in two pools: one with a large variance, located in the type I cells was increased after sympathectomy, the other, more constant, located in the sympathetic nerve endings was entirely depleted after sympathectomy. Section of the carotid sinus nerve increased dopamine and noradrenaline and quadrupled the serotonin content of the CB. It is proposed that carotid sinus and sympathetic innervations regulate the monoamine metabolism of the CB.     

人胚胎大脑海马发育的超微结构研究

本文借助电子显微镜技术对４ 月胎龄组及６ 月胎龄组水囊引产胎儿海马中段部位的神经细胞进行了超微结构观察、拍照,并对照片给予分析、讨论。结果显示：６ 月组部分神经细胞中细胞器较４ 月组发达。该结果可提示人胎儿海马发育中期（４ 月组） 神经细胞功能欠活跃,而到了较晚期（６ 月组） 神经细胞功能增强,细胞器发育较完善,功能活跃。     

人胎听皮质含生长抑素神经元的发育

用免疫组织化学ABC法,研究了16周至新生儿听皮质含SS神经元的发育.含SS神经元最早出现在24周,少数散在的含SS神经元分布在脑室下层、套层,多数分布在皮质Ⅳ到Ⅵ层.随后向浅层发育.提示发育顺序似从深层向浅层发育,深层含SS神经元发育、分化、成熟比浅层早.含SS神经元的胞体平均截面积随发育过程逐渐增大,但不匀速.低胎龄,突起数少而短,双极和多极神经元比例接近,随胎龄增大,多极神经元逐渐比例增高.皮质和皮质下白质散在分布合SS神经纤维.对新生儿听皮质各层含SS神经元进行灰度分析,听皮质含SS神经元的灰度从浅层到深层渐减.提示含SS神经元的活性深层比浅层高.含SS神经元的数量随胎龄增大呈增加趋势,孕期终末增幅明显,可能是发育活跃期,可能与生后语言功能发育有一定关系.     

Morphogenesis of intrahepatic bile ducts of the human fetus

Summary The development of the intrahepatic bile ducts of the human fetus was investigated by light and electron microscopy. Bile canaliculi with microvilli and junctional complexes are already found in the embryo of 7 mm. Some of them are of the intracellular type. At six to seven weeks, large bile canaliculi bounded by four to seven liver cells appear. Subsequently, bile canaliculi are formed predominantly between three to four adjoining liver cells and this arrangement persists throughout later fetal life.The early intrahepatic bile ducts develop around the portal vein as epithelial cell plates derived from the hepatic duct and the branches sprout from the epithelial cell plates in several different places. The epithelial cell plates are separated from each other by primitive connective tissue and they change into a complex network of bile ducts. Formation of the intrahepatic bile ducts is completed by three months.Biliary duct cells at the end of the developing bile ducts are thought to transform into liver cells. Therefore, at the ducts of Hering various transitional cells appear between biliary duct cells and liver cells.The fine structure of the developing liver cells and biliaryduct cells is also described.     

Modulatory effects of histamine on cat carotid body chemoreception

Histamine has been proposed to be an excitatory transmitter between the carotid body (CB) chemoreceptor (glomus) cells and petrosal ganglion (PG) neurons. The histamine biosynthetic pathway, its storage and release, as well as the presence of histamine H1, H2 and H3 receptors have been found in the CB. However, there is only indirect evidence showing the presence of histamine in glomus cells, or weather its application produces chemosensory excitation. Thus, we studied the histamine immunocytochemical localization in the cat CB, and the effects of histamine, and H1, H2 and H3 receptor blockers on carotid sinus nerve (CSN) discharge, using CB and PG preparations in vitro. We found histamine immunoreactivity in dense-cored vesicles of glomus cells. Histamine induced dose-dependent increases in CSN discharge in the CB, but not in the PG. The H1-antagonist pyrilamine reduced the CB responses induced by histamine, the H2-antagonists cimetidine and ranitidine had no effect, while the H3-antagonist thioperamide enhanced histamine-induced responses. Present data suggests that histamine plays an excitatory modulatory role in the generation of cat CB chemosensory activity.     

Specific localization of manserin peptide in the rat carotid body

The carotid body, located at the bifurcation of the common carotid artery, is a small sensory organ that detects changes in oxygen concentration and plays a vital role in controlling respiration. Although several molecules, such as neurotransmitters and neuropeptides, are involved in the regulation of the respiratory system, their detailed mechanisms have not been established yet. This study identifies that the presence of manserin, a neuropeptide, in the carotid body may play a crucial role in regulating respiration.The carotid bodies of adult Wistar rats were perfused with paraformaldehyde, and the frozen sections were subjected to immunohistochemical analyses. The carotid body comprises two distinct types of cells, neuron-like glomus cells and glial-like sustentacular cells. We used specific antibodies to distinguish the specific location of manserin in the carotid body, which included a tyrosine hydroxylase-positive antibody for glomus cells and an S100 protein antibody for sustentacular cells. Immunofluorescence analysis revealed that while tiny, round signals were exclusively observed in the cytoplasm of glomus cells, no signals were observed in sustentacular cells.Because manserin is believed to be secreted from precursor proteins by the endoproteolytic processing of a large precursor protein called secretogranin II, manserin secretion systems may exist in the carotid body, and thus, behave as potential regulators of respiration in the carotid body.