Evidence for the innervation of the puborectalis muscle by the levator ani nerve.
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Humans↗
Biomedical subjects
M C DeRuiter
Publications and source records attributed to M C DeRuiter.
Decellularization of rat aortic valve allografts reduces leaflet destruction and extracellular matrix remodeling.
OBJECTIVES: Decellularization of aortic valve allografts in advance of transplantation is a promising approach to overcome immune-induced early graft failure. In this study the effects of in vitro cell extraction on extracellular matrix molecules and in vivo remodeling of decellularized aortic valves were investigated in a heterotopic aortic valve rat implantation model. METHODS: Rat aortic valve conduits were decellularized by a 2-step detergent-enzymatic extraction method involving sodium dodecyl sulfate in combination with RNase and DNase. Cellular and acellular allogeneic (2x, n = 4) and syngeneic valve grafts (2x, n = 3) were grafted infrarenally into the descending aorta for 21 days. Immunohistochemical techniques were used to study extracellular matrix constitution (elastin, collagen, fibronectin, and chondroitin sulfate) and cellular infiltration. RESULTS: The decellularization procedure resulted in a complete loss of all cellular structures from the entire valve conduit with minimal damage to the extracellular matrix. All transplanted cellular allografts became deformed, swollen, and acellular with major changes in extracellular matrix structure. The transplanted decellularized allografts, however, retained normal preserved valve leaflets comparable to transplanted cellular and acellular syngeneic grafts. With the exception of cellular syngeneic grafts, all other grafts showed retrovalvular thrombi. CONCLUSIONS: Damage to the valves caused by decellularization technique is much less than the damage caused by the recipient's immune response. In vitro removal of viable cells in (cryopreserved) homografts may decrease graft failure. Seeding with autologous or major histocompatibility complex-matched donor endothelial cells will be necessary to diminish damage induced by an absent blood-tissue barrier.
Animals↗
Nerve sparing radical hysterectomy: latest developments and historical perspective.
Autonomic nerve damage during surgery is thought to play a crucial role in the aetiology of bladder dysfunction, sexual dysfunction and colorectal motility disorders which are seen in patients after radical hysterectomy. In order to prevent these complications, Japanese gynaecologists introduced a surgical technique with preservation of the pelvic autonomic nerves in the 1960s. In the 1980s the first English paper was published. Since then several surgical approaches have been described, i.e. liposuction, electrical stimulation to locate nerves intra-operatively and laparoscopically assisted techniques. Recently, more attention is being paid to the importance of sparing the sympathetic hypogastric nerve. All authors report results on small cohorts of patients. The incidence of urinary dysfunction seems very low after nerve sparing. Sparing the autonomic nerves during radical hysterectomy seems feasible and safe in both Japanese and Western patients. Literature review does not provide strong clues for a compromised radicality and cure due to nerve sparing. Future larger clinical trials will have to decide whether the technique of nerve sparing radical hysterectomy could be implemented as a standard treatment for cervical cancer patients.
Autonomic Pathways↗
Normal development of the pulmonary veins in human embryos and formulation of a morphogenetic concept for sinus venosus defects.
A sinus venosus defect is a form of interatrial communication associated with abnormal drainage of the right pulmonary veins. Its morphogenesis still remains unclear. We therefore studied the normal development of pulmonary veins in human embryos in relation to the sinus venosus and the dorsal mesocardium using graphic reconstructions and HNK-1 immunohistochemistry. Twenty embryos, ranging from 4 to 7 weeks' gestation, were examined. At 4 weeks, the orifice of the nonlumenized common pulmonary vein is visible as an endothelial invagination within the sinus venosus segment. Development of the muscular septum primum and the ventral proliferation of extracardiac mesenchyme from the dorsal mesocardium positions the common pulmonary vein (CPV) eventually into the left atrium. The right wall of the CPV contributes to the posterior part of the atrial septum and is continuous with the dorsal sinuatrial fold (the future left venous valve). With the use of HNK-1 antigen expression as a marker for sinus venosus myocardium, this common wall between the right-sided sinus venosus and the CPV is demonstrated, and at 7 weeks the proximal part of the right upper pulmonary vein also becomes part of this common wall. This study demonstrates that the CPV develops within the sinus venosus segment and that later a common myocardial wall is present between the sinus venosus in the right atrium and the CPV. A deficiency of this wall explains the development of sinus venosus defects.
CD57 Antigens↗
Nerve-preserving aortoiliac reconstruction surgery: anatomical study and surgical approach.
OBJECTIVE: Dysfunctional ejaculation and, to a lesser extent, dysfunctional erection caused by disruption of efferent sympathetic pathways is a common complication after aortoiliac reconstruction surgery. The aim was to give an anatomic motivation for a nerve-preserving approach on the basis of right-sided unilateral disruption of lumbar splanchnic nerves. METHODS: Anatomic and microscopic analysis of preaortic and para-aortic retroperitoneal regions in human cadavers was performed. Anatomic analysis was conducted of two aortoiliac reconstruction operations performed on human cadavers; one was performed according to a single-blind procedure, the second with a modified procedure. RESULTS: The lumbar splanchnic nerves supplying the superior hypogastric plexus from the right side were found to be less voluminous than the left-sided ones. The superior hypogastric plexus was found slightly shifted to the left of the midsagittal plane across the abdominal aorta and its bifurcation. Microscopic analysis revealed a thin fascia between the aorta and the subperitoneal tissue compartment. This fascia was used as a plain of dissection to mobilize the preaortic nerve-plexuses without damage from the aortic wall. Analysis of the specimens operated on showed a significant difference in nerve disruption. The standard procedure caused total disruption of the superior hypogastric plexus and extensive disruption of the inferior mesenteric plexus. The modified procedure only caused right-sided unilateral disruption of lumbar splanchnic nerves. CONCLUSION: The autonomic nerves supplying the bladder neck, the vas deferens, and the prostate are closely related to the abdominal aorta and its bifurcation. Right-sided unilateral disruption of lumbar splanchnic nerves without further damage to nervous structures would ensure at least one functional sympathetic pathway remaining after aortoiliac reconstruction surgery.
Aorta, Abdominal↗
Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus.
Prx1 (MHox) and Prx2 (S8) are non-clustered homeobox genes that are expressed in a complex, mostly mesenchyme-specific pattern throughout embryogenesis. The expression pattern and gene-targeted mice previously revealed a major role for Prx1 in skeletogenesis. In addition, specific and high expression of both Prx genes was reported in the developing cardiovascular system, predominantly in prospective connective tissues of the heart and in the great arteries and veins. We examined embryos of previously generated gene-targeted mice. Prx2-/- mutants were viable and did not show cardiovascular malformations. Intracardiac morphology of Prxl-/- and Prx1/Prx2-combined null mutants also appeared normal throughout development. However, the Prx1-/- and Prx1/Prx2 double-null mutants showed a vascular abnormality with an abnormal positioning and awkward curvature of the aortic arch in addition to a misdirected and elongated ductus arteriosus, and in two of seven combined mutants, an anomalous retro-oesophageal right subclavian artery. Generally, all great arteries appeared to run somewhat tortuously through the surrounding mesenchyme. The vascular histology and vessel wall thickness were normal in all mutants. Prx1-/- and Prx double-gene-targeted mice revealed similar spectra of vascular anomalies, but double mutants appeared to be more seriously affected. The current findings suggest that other genes may compensate for the loss of Prx in the heart, but, in contrast, our data support a role for Prx in the development of vascular and perivascular matrix.
Animals↗
HNK-1 expression patterns in the embryonic rat heart distinguish between sinuatrial tissues and atrial myocardium.
HNK-1 expression was studied by immunohistochemistry in serial sections of embryonic and fetal rat hearts from 11.5 to 16.5 embryonic days. Graphic reconstructions were made to obtain detailed 3D information on the localization of immunoreactive tissues. The antibody used appeared to stain most parts of the venous sinus and the sinuatrial transitional zone as well as the atrioventricular transitional zone, but the patterns varied through the different developmental stages. At 11.5 days, positive myocardium was found in the right atrium and on top of the ventricular septal primordium. At 13.5 days, the left venous valve and the posterior atrial wall containing the orifice of the pulmonary vein were immunoreactive, and so were the right venous valve, the septum spurium and the superior, right-lateral and inferior parts of the atrioventricular canal. From the latter, immunoreactivity continued onto the crest of the ventricular septum. At 15.5 days, HNK-1 positivity in the two venous valves had become continuous, whereas the right-lateral part of the atrioventricular canal had lost its positivity, thus making the positive areas in the superior and inferior parts of this canal discontinuous. From the venous valves immunoreaction continued into the venous sinus septum but this area remained discontinuous with the inferior part of the atrioventricular canal. It is concluded that the entirety of venous sinus and sinuatrial transitional zone expresses the HNK-1 antigen and that the orifice of the pulmonary vein belongs to this complex, rather than to the embryonic atrium proper, which is HNK-1 negative. Extrapolation of these data to the adult human atrium leads to the conclusion hat most "atrial septal structures" are of sinuatrial origin, leaving the flap valve of the oval fossa (atrial septum primum) as the only really atrial structure. It is suggested that the atrioventricular node is derived from the inferior portion of the atrioventricular canal, and that two expansions of sinuatrial tissue form the substrate for anterior and posterior atrionodal inputs which in the literature have been described as internodal tracts.
Animals↗
Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression: possible relevance for understanding of abnormal atrial automaticity.
BACKGROUND: Abnormal atrial automaticity in young patients with structurally normal hearts is often located around the pulmonary veins and in sinus venosus-related parts of the right atrium. We hypothesize that these ectopic pacemaker sites correspond to areas of embryonic myocardium with an early phenotypic differentiation, as indicated by differences in antigen expression during normal cardiac development. METHODS AND RESULTS: In human embryos ranging in age from 42 to 54 days of gestation, the development of the cardiac conduction system was studied with the use of HNK-1 immunohistochemistry. HNK-1 stains the developing atrioventricular conduction system, ie, the bundle branches, His bundle, right atrioventricular ring, and retroaortic ring. In addition, the myocardium around the common pulmonary vein showed transient HNK-1 antigen expression. In the right atrium, 3 HNK-1-positive connections were demonstrated between the sinoatrial node and the right atrioventricular ring. An anterior tract through the septum spurium connects the sinoatrial node with the anterior right atrioventricular ring, and 2 posterior tracts connect the sinoatrial node with the posterior right atrioventricular ring through the right venous valve (future crista terminalis) and sinus septum, encircling the coronary sinus. The medioposterior part of the right atrioventricular ring connected to the His bundle and the medioanterior part form 2 node-like structures. CONCLUSIONS: In patients with abnormal atrial automaticity, the distribution of left and right atrial pacemaker foci correspond to areas of the embryonic myocardium that temporarily express the HNK-1 antigen.
Atrioventricular Node↗
Comparative anatomy and ontogeny of the ductus arteriosus, a vascular outsider.
In its function of separating pulmonary and systemic arterial blood flow, the ductus arteriosus, which connects both circuits, either closes permanently at a certain stage in development or attains a capacity to close and reopen depending on the physiological needs in certain species. In air-breathing vertebrates varying from lungfish to mammals, the ductus arteriosus derives from the sixth pharyngeal arch artery, and in preparation for its specific task, undergoes its own unique differentiation programme, starting early in development. To date, the mechanisms involved in defining this unique status, as compared to the other great arteries, are unclear. This review clarifies some of the elusiveness of the ductus arteriosus. It includes a comparative description of this artery in species exemplifying the different classes of air-breathing vertebrates, and illustrates similarities and differences in morphogenesis and closure mechanisms among the species. It also deals with possible influences of vascular innervation and with congenital anomalies in which the ductus arteriosus is involved. New data suggest that HOXB5 expression in the neural crest along the dorsal half of the sixth arch artery may be involved in the instigation of ductus arteriosus differentiation.
Animals↗
Extraembryonic venous obstructions lead to cardiovascular malformations and can be embryolethal.
OBJECTIVE: To expand our knowledge concerning the effect of placental blood flow on human heart development, we used an embryonic chicken model in which extraembryonic blood flow was manipulated. METHODS: First, one of the three major vitelline veins was ligated, while blood flow was visualized with Indian ink. In this way, we could study the effect of different ligation positions on intracardiac flow patterns. Secondly, these vitelline veins were ligated permanently with a microclip until cardiac septation was completed, thereafter, the hearts were morphologically evaluated. In this way, we could study the impact of the ligation position on the severity and frequency of heart malformations. On combining the results, we were able to study the effect of different intracardiac flow patterns on heart development. RESULTS: Although ligation of each vein resulted in different intracardiac flow patterns, long-term ligation resulted in similar cardiovascular malformations in survivors. These consisted mainly of ventricular septum defects (VSDs), semilunar valve anomalies, and pharyngeal arch artery malformations. There was no significant difference (p > 0.05) between the ligation position and the incidence of cardiovascular malformations. However, the percentage mortality after clipping the left lateral vitelline vein was significantly higher (p < 0.05) than after ligation of either the right lateral or posterior vitelline vein. CONCLUSIONS: Early extraembryonic venous obstruction leads to altered flow patterns, which probably result in shear stress changes. In postseptation stages, these result in a spectrum of cardiovascular malformations irrespective of the ligation position. A diminished incidence of VSDs in the oldest stage was attributed to delayed closure of the interventricular foramen.
Animals↗
Unique vascular morphology of the fourth aortic arches: possible implications for pathogenesis of type-B aortic arch interruption and anomalous right subclavian artery.
OBJECTIVE: Neural crest-derived cells were previously shown to participate in vessel wall formation of the great thoracic arteries, and their contribution was proposed to affect morphology and physiology of these vessels in the chick. The present investigation was undertaken to examine vascular differentiation and morphogenesis of the neural crest-derived aortic arches in mammals. METHODS: Using immunohistochemical markers for smooth muscle cell differentiation and a neurofilament marker, we examined morphogenesis of the great arteries in mice, ranging from embryonic day 11.5 to the adult. RESULTS: We observed that in the 4th aortic arch arteries early media formation differed from the other arteries, in that they almost completely lacked (or showed decreased) actin expression in certain areas. This discontinuity in actin expression persisted throughout much of foetal development, in the form of circular segments of cells displaying decreased staining for smooth muscle markers, both at the left and right side of the arterial tree. In adult mice, the 4th arch artery derivatives, segment B of the aortic arch and the proximal right subclavian artery, were observed to differ from adjoining vessels in their smooth muscle and elastic composition. Staining for neurofilaments revealed close association of the developing segments with apparent sensory afferent vascular innervation. CONCLUSION: The unique areas of the 4th arch artery identified here reflect the basic segmental patterning of the early embryonic pharyngeal arches. These segments correlate with sites that are predisposed to interruption or severe hypoplasia, and may thus reveal part of the aetiology of type-B aortic arch interruptions and arteria lusoria.
Actins↗
Altered hemodynamics in chick embryos after extraembryonic venous obstruction.
OBJECTIVE: To obtain insight into hemodynamics during abnormal cardiac development, a chick model was developed recently in which a spectrum of conotruncal anomalies, in combination with abnormal semilunar valves and/or pharyngeal arch artery malformations, was induced through extraembryonic venous obstruction (venous clip) at stage 17 (70-h incubation). METHODS: In chick embryos of stage 24 and stage 34 control (n = 8; n = 21) and with venous clip (n = 11; n = 18), we simultaneously measured dorsal flow velocities with a 20-MHz pulsed Doppler velocity meter and dorsal aortic (stage 24) and vitelline artery (stage 34) blood pressures with a servo-null system. After the hemodynamic recordings were collected, all 58 embryos were subjected to morphological examination. The hemodynamic data were correlated with the morphology. Statistical comparison was performed between control and experimental values. RESULTS: At stage 24, venous clip embryos showed impaired looping. Physiologically, only a decrease in peak acceleration was found in these embryos (p < 0.05). At stage 34, a spectrum of conotruncal malformations was seen, that consisted of a ventricular septal defect in combination with abnormal semilunar valves and/or pharyngeal arch malformations. A dextroposed aorta in combination with a ventricular septal defect was diagnosed as double-outlet right ventricle. Hemodynamically, peak systolic and mean velocities, peak systolic and mean blood flows and stroke volume were increased while the heart rate was reduced after placement of the venous clip (p < 0.05). In both stages, pressure readings showed no statistically significant differences between control and experimental embryos. CONCLUSION: Our findings suggest that the hemodynamic changes seen in venous clip embryos reflect the presence of a compensatory mechanism.
Animals↗
Smooth muscle cell origin and its relation to heterogeneity in development and disease.
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Animals↗
Neural crest cell contribution to the developing circulatory system: implications for vascular morphology?
In this study, the distribution patterns of neural crest (NC) cells (NCCs) in the developing vascular system of the chick were thoroughly studied and examined for a correlation with smooth muscle cell differentiation and vascular morphogenesis. For this purpose, we performed long-term lineage tracing using quail-chick chimera techniques and premigratory NCC infection with a replication-incompetent retrovirus containing the LacZ reporter gene in combination with immunohistochemistry. Results indicate that NCC deposition around endothelial tubes is influenced by anteroposterior positional information from the pharyngeal arterial system. NCCs were shown to be among the first cells to differentiate into primary smooth muscle cells of the arch arteries. At later stages, NCCs eventually differentiated into adventitial fibroblasts and smooth muscle cells and nonmuscular cells of the media and intima. NCCs were distributed in the aortic arch and pulmonary arch arteries and in the brachiocephalic and carotid arteries. The coronary and pulmonary arteries and the descending aorta, however, remained devoid of NCCs. A new finding was that the media of part of the anterior cardinal veins was also determined to be NC-derived. NC-derived elastic arteries differed from non-NC elastic vessels in their cellular constitution and elastic fiber organization, and the NC appeared not to be involved in designating a muscular or elastic artery. Boundaries between NC-infested areas and mesodermal vessel structures were mostly very sharp and tended to coincide with marked changes in vascular morphology, with the exception of an intriguing area in the aortic and pulmonary trunks.
Animals↗
Patterns of paired-related homeobox genes PRX1 and PRX2 suggest involvement in matrix modulation in the developing chick vascular system.
PRX1 (MHox) and PRX2 (S8) were previously shown to be expressed throughout embryogenesis in complex, mostly mesenchyme-specific patterns. In the developing cardiovascular system both genes were highly expressed in prospective connective tissues, that is, endocardial cushions and valves, the epicardium, and the wall of the great arteries and veins. We further scrutinised expression of PRX1 and PRX2 in the developing vascular system of the chicken embryo and compared patterns with those of established vascular differentiation markers (muscle-actin, procollagen I, and fibrillin-2). PRX1 and PRX2 expression were associated with the primary vessel wall from early stages onward and became increasingly restricted to the adventitial and outer medial cell layers. PRX1 eventually colocalised strikingly with procollagen I and fibrillin-2 expression and generally excluded high smooth muscle actin expression. Furthermore, PRX1 expression preceded the segregation of very distinct nonmuscular cells and smooth muscle cells in the media of the great arteries. PRX2 patterns deviated at later stages from those of PRX1 and showed specific and high transcript levels in the ductus arteriosus from embryonic day 6 onward. Results suggest that PRX genes are not essential in smooth muscle contractile differentiation, but may be involved in matrix modulation in the vascular system and possibly in defining the noncontractile cellular phenotype and in media-adventitia definition.
Animals↗
Development of the atrioventricular valve tension apparatus in the human heart.
Using various microscopical techniques we studied the development of the atrioventricular valves in human hearts between 5 and 19 weeks of development. Within the atrioventricular cushions two different layers could be recognized that remained present in all ages studied. The atrial layer, being present at the side of the atrioventricular orifice, was positive for laminin while the ventricular layer, that was connected to the myocardium, was positive for fibronectin and collagen III. Fate-mapping of these two layers, morphometrics, and scanning electron microscopy, supplemented with in vivo labeling of cushion tissue in chicken hearts have lead to new insights in the process of valve development. The cushions became freely movable prevalvular leaflets by delamination of ventricular myocardium underneath the cushion tissue. This myocardium gradually retracted towards annulus and papillary muscles and finally disappeared, resulting in fibrous, non-myocardial valves. The atrial layer of the cushions remained present as a jelly-like surface on the valve leaflets while the ventricular layer of the cushions became the compact fibrous tissue of the leaflets and the chords. Chordal development was first visible at 10 weeks of development when gaps were formed in the ventricular layer of the cushions on top of the papillary muscles. These gaps enlarged into the interchordal spaces while the cushion tissue in between the gaps lengthened to form the chords. We conclude that the leaflets as well as the chords of the atrioventricular valves are derived from atrioventricular cushion tissue. Myocardium is only important for loosening of the leaflets while keeping connection with the developing papillary muscles. Errors in delamination or retraction of myocardium or remodeling of cushion tissue into chords form the basis for various congenital valve anomalies.
Embryonic and Fetal Development↗
Embryonic endothelial cells transdifferentiate into mesenchymal cells expressing smooth muscle actins in vivo and in vitro.
All blood vessels are lined by endothelium and, except for the capillaries, surrounded by one or more layers of smooth muscle cells. The origin of the embryonic vascular smooth muscle cell has until now been described from neural crest and locally differentiating mesenchyme. In this study, we have substantial evidence that quail embryonic endothelial cells are competent in the dorsal aorta of the embryo to transdifferentiate into subendothelial mesenchymal cells expressing smooth muscle actins in vivo. At the onset of smooth muscle cell differentiation, QH1-positive endothelial cells were experimentally labeled with a wheat germ agglutinin-colloidal gold marker (WGA-Au). No labeled subendothelial cells were observed at this time. However, 19 hours after the endothelial cells had endocytosed, the WGA-Au-labeled subendothelial mesenchymal cells were observed in the aortic wall. Similarly, during the same time period, subendothelial cells that coexpressed the QH1 endothelial marker and a mesenchymal marker, alpha-smooth muscle actin, were present. In such cells, QH1 expression was reduced to a cell membrane localization. A similar antigen switch was also observed during endocardial-mesenchymal transformation in vitro. Our results are the first direct in vivo evidence that embryonic endothelial cells may transdifferentiate into candidate vascular smooth muscle cells. These data arouse new interpretations of the origin and differentiation of the cells of the vascular wall in normal and diseased vessels.
Actins↗
Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo.
To study the role of blood flow in normal and abnormal heart development, an embryonic chicken model was developed. The effect of altered venous inflow on normal intracardiac blood flow patterns was studied by visualization of blood flow with India ink. At stage 17, India ink was injected into a capillary or small venule within a specific yolk sac region. After determination of the normal intracardiac flow pattern, the right lateral vitelline vein was ligated, and the new intracardiac flow pattern was studied. Ligation resulted in disturbance of normal intracardiac flow patterns, which was most obvious in the conotruncus. The long-term effect of these abnormal intracardiac flow patterns on the development of the heart and pharyngeal arch arteries was investigated by permanent ligation in ovo with a microclip at stage 17 and subsequent evaluation at stages 34, 37, and 45. These experiments revealed anomalies of the vascular system in 58 of the 91 ligated embryos studied. We observed intracardiac malformations consisting of subaortic ventricular septal defects (n = 52), semilunar valve anomalies (n = 19), atrioventricular anomalies (n = 7), and pharyngeal arch artery malformations (n = 32). It is concluded that abnormal intracardiac blood flow, resulting from hampered venous inflow, may result in serious intracardiac and pharyngeal arch artery malformations comparable to defects observed in embryonic chicken models subjected to neural crest ablation, cervical flexure experiments, and excessive retinoic acid treatment.
Animals↗