The atrioventricular valves of the guinea-pig. I. A light microscopic study

The atrioventricular valves contain dense plexuses of adrenergic nerve fibers, derived from atrial and ventricular sources. Most of the adrenergic terminals are located in the lower third of the cusps. This region, which contains adrenergic terminals and acetylcholinesterase-positive nerve endings is devoid of muscle fibers and blood vessels. The acetylcholinesterase-positive endings may be sensory; and norepinephrine released from the adrenergic terminals may influence their performance. In the mitral valve, the atrial adrenergic plexus is separated from the ventricular plexus by a narrow zone that is free of adrenergic nerves. In most other respects the innervation, musculature and vascular supply of the mitral valve is similar to that of the tricuspid valve. Each valve has an intrinsic skeleton. This is made up of collagenous “ribs” that pass up from the chordae tendineae and fan out in the cusps. “Ribs” from adjacent chordae overlap and interweave, forming a complex support system. The musculature of the valves is complex and seems to have several functions. The annular muscle around the valve orifice may act as an atrioventricular sphincter, while offshoots that insert into the collagenous “ribs” of the cusp may assist the papillary muscles in maintaining tension on the cusps. The meshwork of muscle fibers between “ribs” may prevent ballooning of the cusps during systole. We found no consistent association between valvar muscles and nerves. Blood vessels are restricted mainly to the upper muscular part of the cusps, although a few capillary loops descend into the midzone of the cusps.     

Design of heart valves: A review

Each of the major cardiac valves (two arterial and two atrioventricular) is made up of a fibrous annulus with a characteristic configuration, and cusps or leaflets comprising a layer of endocardium folded over a fibrous lamina. Each of the arterial valves (aortic and pulmonary) has an annulus shaped like a three-pronged coronet to which are attached three equal-sized semilunar cusps. The arterial wall beyond each cusp forms a pocket or sinus which is crucial in the efficient closure of these valves. The coronary arterial orifices in the aorta lie high in two of the sinuses or above them and are unaffected by valve action. Narrowing of the annulus is a significant component of closure of each cardiac valve, more so for the atrioventricular valves than the arterial. Despite their traditional terminology, the left and right atrioventricular valves (mitral and tricuspid) both possess more than three leaflets each. Closure of these valves is not dependent on the number of leaflets and it is easiest to regard leaflet tissue as a continuous veil or skirt tapering towards the ventricles, where it is tethered to papillary muscles by means of chordae tendineae. Closure of these valves is biphasic, an incomplete phase in late diastole and complete closure during ventricular systole. Movement of atrioventricular leaflet tissue is slight as it is held down by tension of the chordae tendineae. © 1993 Wiley-Liss, Inc.     

Variations in atrioventricular valve innervation in four species of mammals

In this series of studies, the innervation patterns of whole-mount preparation of bicuspid and tricuspid valves were studied by light microscopy in the mouse, rat, guinea pig, and opossum. The acetylcholinesterase-positive networks of nerve fibers showed many similarities in the basic patterns of valve innervation in all of the species studied, but several interspecies variations were observed. The basal zone of the valve adjacent to the fibromuscular atrioventricular ring displayed the most dense plexus of nerves, with acetylcholinesterase-positive fibers being seen across the width of the valve. In the intermediate zone of the valve, less dense plexuses of nerve fibers were found; and these were more numerous in the cuspal areas and less numerous in the intervening commissural areas. In the distal portions of the valve, nerve networks arborized extensively, with some of their nerve fibers extending toward the chordae tendineae and the free edges of the valve cusps. Only in the guinea pig and opossum did these fibers reach the free margin of the valve cusp, where they either ended directly as free nerve endings or lay parallel to the free edge of the cusp, often running between adjacent chordae tendineae. Although the patterns of innervation were similar in both bicuspid and tricuspid valves, the innervation density of the bicuspid valve was greater than that of the tricuspid valve for each species examined. A distinguishing feature of guinea pig and opossum tricuspid valves was that their chordae tendineae were relatively more prominent and more densely innervated than the bicuspid chordae tendineae. Free nerve endings with no light microscopic evidence of specialization were present throughout the bicuspid and tricuspid valves of all species studied. Some nerve endings in the opossum showed evidence of specialization, with brush-like arborizations leading to presumed free terminals seen chiefly in the distal zone of the valve cusps. Although some general tendencies were apparent, we have demonstrated that interspecies heterogeneity exists in the terminal networks of the atrioventricular valves of mouse, rat, guinea pig, and opposum. In spite of the questions raised regarding the significance of valve innervation in light of the success of valve prostheses, there is relatively high morbidity and mortality associated with heart valve replacement, partly due to deterioration in ventricular function. We and other investigators have reported that valvar nerves extend to the chordae and papillary muscles, varying with valve and species. This anatomical information about normal valves helps to lay the foundation for future studies of the role of valve innervation in the regulation of cardiac function and dysfunction. Such knowledge should be applicable for the control and management of myocardial infarction, valve disease, valve replacement, valvuloplasty, cardiac transplantation, administration of drugs, etc.     

Distribution of PGP 9.5, TH, NPY, SP and CGRP immunoreactive nerves in the rat and guinea pig atrioventricular valves and chordae tendineae

The distribution of nerves immunoreactive to protein gene product 9.5 (PGP 9.5), tyrosine hydroxylase (TH), neuropeptide Y (NPY), substance P (SP) and calcitonin gene related peptide (CGRP) antisera was investigated in the atrioventricular valves of the Sprague–Dawley rat and the Dunkin–Hartley guinea pig using confocal and epifluorescence microscopy. No major differences were noted between the innervation of the mitral and tricuspid valves in either species. For all antisera the staining was more extensive in the guinea pig valves. Two distinct nerve plexuses separated by a ‘nearly nerve free’ zone were identified in both species with each antiserum tested. This was most apparent on the anterior cusp of the mitral valve. The major nerve plexus extends from the atrioventricular ring through the basal, intermediate and distal zones of the valves towards the free edge of the valve cusp. These nerve bundles, arranged as primary, secondary and tertiary components, ramify to the free edge of the valve and extend to the attachment of the chordae. They do not contribute to the innervation of the chordae tendineae. The second, minor chordal plexus, runs from the papillary muscles through the chordae tendineae and passes parallel to the free edge of the cusp. The nerves of this minor plexus are interchordal, branching to terminate mainly in the distal zone, free edge of the valve cusp and adjacent chordae tendineae. Some interchordal nerve fibres loop from a papillary muscle up through a chorda, along the free edge and pass down an adjacent chorda into another papillary muscle. The nerve fibres of the major and minor plexuses intermingle although no evidence was found for interconnectivity between them. In the distal zone between the major plexus which extends from the base of the valve and the minor chordal plexus there is a zone completely free of nerves staining with antisera to TH and NPY. Occasional nerves which stained positive for PGP 9.5, SP and CGRP immunoreactivities crossed this ‘nearly nerve free zone’ passing either from the chordal/free edge nerves to the intermediate and basal zones or vice versa. An additional small nerve plexus which displayed immunoreactivity to CGRP antiserum extended from the atrioventricular ring into the basal zone of the valve cusp. Not all chordae tendineae displayed immunoreactive nerve fibres. It is concluded that the innervation patterns of the sensory and sympathetic neurotransmitters and neuropeptides examined in the atrioventricular valves of the rat and guinea pig are ubiquitous in nature. The complexity of the terminal innervation network of the mammalian atrioventricular valves and chordae tendineae may contribute to the complex functioning of these valves in the cardiac cycle.     

Muskuläre Sehnenfäden in der linken Herzkammer

Zusammenfassung Die Chorda muscularis persistens stellt eine Hemmungsmißbildung am Segelklappensystem dar. Sie kommt hauptsächlich am vorderen Papillarmuskel des linken Ventrikels vor. In den meisten Fällen stellt sie ein harmloses Relikt dar. Gelegentlich kann sie aber bei massiver Einstrahlung in das Klappengewebe ernste funktionelle Störungen des Klappenschlusses in Form einer Insuffizienz bewirken. Bei Vorliegen einer Mitralinsuffizienz mit unklarer Genese sollte auch an diese Anomalie gedacht werden.

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Muscular chordae tendineae of the left cardiac ventricle

Summary The Chorda muscularis persistens, an arrest of development, is a variation of the connection between the papillary muscles and the valve cusps whereby the papillary muscle is connected with the valve cusp without a chorda tendinea. It is chiefly found on the musculus papillaris anterior of the left ventricle. The usually harmless chorda muscularis persistens occasionally may cause insufficiency of the mitral valve if fibers of the papillary muscle merge with the structure of the valve cusps. In every case of a mitral insufficiency of occult cause this anomaly should be considered.

     

Floppy mitral valve chordae tendineae: histopathologic alterations

Pathologic studies of floppy or myxomatous mitral valves have focused primarily on changes in the valve cusps, with little attention given to the chordae tendineae. In a systematic study of the histopathology of floppy mitral valve chordae tendineae, 128 nonruptured chordae from 8 severely regurgitant floppy mitral valves were compared to 152 chordae from 10 normal control mitral valves and to 152 chordae from 8 control mitral valves with severe regurgitation due to ischemic heart disease. Collagen alterations were observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 38% of floppy mitral valve chordae. Moderate or severe acid mucopolysaccharide accumulation was observed in 2% of normal mitral valve chordae and 3% of control regurgitant mitral valve chordae compared to 39% of floppy mitral valve chordae. Nonuniform histopathologic alterations, rare in normal and control regurgitant mitral valve chordae tendineae, were frequent in floppy mitral valve chordae tendineae (p less than 0.001). Histopathologic alterations provide the basis for abnormal physical properties previously demonstrated in floppy mitral valve chordae tendineae and may predispose to chordal elongation and rupture.     

Determination of the pressure required to cause mitral valve failure

A method has been developed for applying water pressure to a closed mitral valve on the side corresponding to the heart's left ventricle. The pressure is increased until fluid flows through the valve, i.e. until it fails. A specific dissection technique has been developed to produce a specimen with two annular rings, mitral annulus and papillary muscle annulus. Since the valve is maintained intact, with its leaflets attached to papillary muscles by the chordae tendineae, this method allows the effects of ruptured chordae and their surgical repair or replacement to be assessed in vitro. The chamber that holds the valve supports both the mitral annulus and papillary muscle annulus of the specimen. The mitral annulus is sutured onto rubber sheeting held in the chamber. The papillary muscle annulus is held in place by a Perspex support. The main part of the apparatus consists of a water pump connected through flexible tubing to the chamber that holds the valve in place. The pressure at failure is measured using a pressure transducer. Preliminary experiments demonstrate that anterior leaflet marginal chordae, but not strut chordae, are vital to valve function. Posterior leaflet chordae have been found to be important for valve competence.     

大鼠心瓣膜神经支配

本文通过对32只大鼠心瓣膜进行胆碱酯酶组织化学法、乙醛酸诱发荧光法及P物质免疫组化方法的观察,获得心瓣膜胆碱能、肾上腺素能及肽能(SP)神经支配全貌。P物质免疫反应阳性神经纤维在房室瓣自瓣膜基部向下及自腱索向上进入瓣膜;在动脉瓣自附着缘进入瓣膜。该纤维的性质及走向提示SP免疫反应阳性神经纤维可能是感受血流动力学变化的传入神经。     

家猪心脏三尖瓣复合体的形态学观测

目的　观测家猪心脏三尖瓣复合体 ,为家猪心脏研究和心脏移植积累资料。方法　甲醛固定的家猪心脏 35例 ,大体解剖并观测三尖瓣复合体。结果　家猪心脏三尖瓣复合体由瓣环、瓣膜、腱索和乳头肌构成 ,瓣环周长为 70 75± 8 4 5mm ,前瓣、后瓣、隔侧瓣、前隔连合、前后连合、后隔连合的高度分别为 14 5 8±2 6 4、14 16± 2 5 0、12 84± 2 37、6 2 9± 1 97、6 86± 1 0 1、6 5 1± 1 36mm。前隔连合、前后连合、后隔连合的宽度分别为 6 4 0± 1 5 4、6 78± 1 2 3、6 4 3± 1 4 6 ;前乳头肌起始 ,腱索附着于前瓣、后瓣和前后连合的条数分别为 3 0 0± 0 97、3 0 9± 1 0 9、2 4 4± 1 16 ;后乳肌起始 ,腱索附着于后瓣、隔侧瓣和后隔连合的条数分别为 2 6 0± 0 6 9、3 0 9± 1 6 3、1 14± 0 4 3。隔侧乳头肌起始 ,附着于前瓣、隔侧瓣、前隔连合的腱索条数分别为1 71± 0 6 7、2 37± 1 2 6、0 94± 0 4 2。结论　家猪心脏三尖瓣复合体中各结构与人类相似 ,但大小有一定差异。     

Structure of chordae tendineae in the left ventricle of the human heart

The bicuspid (mitral) valve complex of the human heart consists of functional units which include the valve leaflets, chordae tendineae and the papillary muscles. The mechanical properties of these functional units depend to a large extent on the link between the muscle and the valve. This link is usually arranged in a branching network of avascular tendinous chordae composed of collagen and elastic fibres, which transmit contractions of the papillary muscle to the valve leaflets. In order to perform their function efficiently, the chordae have to possess a high degree of elasticity, as well as considerable strength and endurance. Human chordae tendineae originating from the left ventricles were obtained from 7 embalmed cadavers and 6 postmortem subjects of various ages. Samples washed in saline were fixed or postfixed in 9% formol saline. Observations were made by illuminating the chordae along their axes. The reflected images originating from the superficial collagenous layers of the relaxed chordae showed a striped pattern 11 μm in width. Scanning electron and light microscopy of the chordae confirmed an undulating pattern of collagen fibrils arranged in bundles of planar waves in register and around the entire circumference of the chorda. The dimensions of the waves correlated with those of the striped reflected pattern. The observed undulating arrangement of the collagen fibrils appears to produce an inherent built-in elasticity which is likely to be of considerable advantage for a tissue which is under continuous repetitive stress. The chordae were covered by endocardium composed of a superficial layer of smooth squamous endothelial cells and an underlying dense layer of elastic fibres. It is suggested that the relaxed striped chordae, consisting of undulating collagen fibrils, straighten when the chordae become stretched by papillary muscle contraction, thereby mitigating the peak stress developed during muscle contraction. On relaxation the elastic tissue tends to return the collagen to its wavy configuration. It is also suggested that the regular wavy pattern of collagen seen in young individuals gradually changes with age by elongation of the wave pattern which eventually becomes randomised. In addition, with increasing age, substantial cushions of connective tissue appear below endocardium while the dense collagenous core has a reduced cross-sectional area which may lead to stretching and eventual rupture of the chordae.     

BMP and FGF regulatory pathways in semilunar valve precursor cells.

In the developing atrioventricular (AV) valve, limb bud, and somites, cartilage cell lineage differentiation is regulated by bone morphogenetic protein (BMP), while fibroblast growth factor (FGF) controls tendon cell fate. We observed aggrecan and sox9, characteristic of cartilage cell types, and scleraxis and tenascin, characteristic of tendon cell types, in developing avian semilunar valves. Addition of BMP4 to outflow tract (OFT) precursor cells of young (E4.5) but not older (E6) chick embryos activated Smad1/5/8 and induced sox9 and aggrecan expression, while FGF4 treatment increased phosphorylated MAPK (dpERK) signaling and promoted expression of scleraxis and tenascin. These results identify BMP and FGF pathways that promote expression of cartilage- or tendon-like characteristics in semilunar valve precursor cells. In contrast to AV valve precursor cells, which diversify into leaflets (cartilage-like) or chordae tendineae (tendon-like), semilunar valve cells exhibit both cartilage- and tendon-like characteristics in the developing and mature valve cusp.     

Mitral and aortic valve abnormalities in a patient with fibrodysplasia ossificans progressiva

A 36-yr-old female with a 20-yr history of fibrodysplasia ossificans progressiva (FOP) died as the result of ruptured gastric ulcers. The patient had been treated with disodium ethane-l-hydroxy-1, 1-diphosphonate (EHDP). Post mortem there was thickening of the aortic valve cusps and mitral valve leaflets as well as shortening and thickening of the chordae tendineae of the mitral valve. This is a previously unreported association.     

Mitral-valve mechanics—stress/strain characteristics of excised leaflets,analysis of its functional mechanics and its medical application

The stress/strain characteristics of mitral-valve leaflets are determined. The leaflet elements exhibit the characteristic nonlinear stress/strain behaviour with a transition point; the posttransition-point modulus being orders of magnitude greater than the pretransition modulus. An element closer to the chordae tendineae has an initial modulus 4–5 times that of an element in the centre of the cusp; its transition point also occurs at a lower strain. These tests provide information on the strength characteristics of the mitral-valve leaflets. Theoretical stress analyses are carried out to determine the range and the limits of adverse stresses that a valve has to withstand in order to obtain design criteria for the prosthetic mitral valve. Analyses and procedures are presented to obtain thein vivo average modulus (stiffness) of the valve leaflet by suitable correlation of the analysis with spectral phonocardiography.     

Quantitative analysis of tenascin in chordae tendineae of human left ventricular papillary muscle with aging.

A computer image analysis was done to investigate the distribution of tenascin and collagenous matrix components (collagen types I and III) in the chordae tendineae of the anterior cusp of the left ventricular papillary muscle, using confocal laser scanning microscopy in both a 20s age group and an 80s-90s age group. Tenascin and the collagenous matrix components showed marked accumulation in the 80s-90s age group with elastic fiber concentration being increased in the same region as that in the 20s age group. The highest content of intersurface layer staining with an anti-tenascin antibody and with anti-collagen type III in the inner layer was found in the 80s-90s age group. These content levels were low in each region in the 20s age group. The distribution and content of these extracellular matrix changes are related to the changes in mechanical performance of the cardiac muscle with age.     

The atrioventricular valves of the guinea-pig. II. An ultrastructural study

Each atrioventricular valve of the guinea-pig consists of a core of connective tissue and muscle covered by endothelial cells. The muscle forms an annulus at the attached margin of the valve adjacent to the fibrous annulus. Some fibers from the lower part of the muscular annulus turn sharply toward the free margin of the valve and form a complex meshwork. These fibers resemble atrial muscle, but are noteworthy in that each contains myofibrils that are oriented in different directions. Some muscle fibers have features similar to those of conducting fibers, i.e., glycogen rich cytoplasm containing few myofibrils. Unmyelinated nerve fibers are numerous in both the mitral and tricuspid valves, but myelinated fibers were found only in the mitral valve. Typical adrenergic terminals were found adjacent to some cholinergic endings. Mitochondria-filled terminals (sensory?) and a third type of motor terminal were present also. Bundles of collagenous fibers extend from the chordae tendineae into the valve cusps where they fan out into small bundles. The other formed elements of the stroma are microfibrils and a flocculent material. There are a few elastic fibers beneath the endothelium. Interstitial cells, many of which possess solitary flagella are scattered throughout the matrix.     

Improved In Vitro Quantification of the Force Exerted by the Papillary Muscle on the Left Ventricular Wall: Three-Dimensional Force Vector Measurement System

Recent developments indicate that the forces acting on the papillary muscles can be a measure of the severity of mitral valve regurgitation. Pathological conditions, such as ischemic heart disease, cause changes in the geometry of the left ventricle and the mitral valve annulus, often resulting in displacement of the papillary muscles relative to the annulus. This can lead to increased tension in the chordae tendineae. This increased tension is transferred to the leaflets, and can disturb the coaptation pattern of the mitral valve. The force balance on the individual components governs the function of the mitral valve. The ability to measure changes in the force distribution from normal to pathological conditions may give insight into the mechanisms of mitral valve insufficiency. A unique in vitro model has been developed that allows quantification of the papillary muscle spatial position and quantification of the three-dimensional force vector applied to the left ventricular wall by the papillary muscles. This system allows for the quantification of the global force exerted on the posterior left ventricular wall from the papillary muscles during simulation of normal and diseased conditions. © 2001 Biomedical Engineering Society. PAC01: 8719Rr, 8719Ff, 8719Hh, 8719Xx, 8710+e     

Contribution to the study of connective fibers in human mitral valve

8 hearts of male and female, white and non-white Brazilians of different ages were studied. The histological arrangement of the collagen and elastic tissue of the leaflets of the left atrioventricular valve was studied. The histological study of the leaflets under polarized light, showed that the collagen from the chordae tendineae fans out in its interior and reaches a fibrous ring from the valve. Specific staining for elastic fibers revealed that these fibers are chiefly concentrated on the free margin of the leaflets. These findings were discussed based on the physiology of the papillary muscle contraction and on the proposed mechanisms of the valve closure.     

The morphology of canine lymphatic valves

The architecture of 60 valves from thoracic ducts and from renal hilar and mesenteric collecting lymph vessels of dogs were studied by scanning electron microscopy as well as by light and transmission electron microscopy. All of the valves seen in hilar and mesenteric lymph vessels and most of those studied in the thoracic duct were bicuspid. An occasional tricuspid and one monocuspid valve was seen in the thoracic duct. The semilunar cusps of the valves extended from the vessel wall, to which they were attached, towards the valve outlet where adjacent cusps fused. Coincident to the area of fusion was the formation of mesenteric-like folds or buttresses that anchored the cusps to the vessel wall. These folds extended 50–100 μm beyond the cusp margins on the outflow side of the valve. The attachments of the cusps, buttresses, and vessel wall to one another resulted in the formation of postvalvular sinuses, such that raised intraluminal pressure downstream to valve areas would distend the sinuses, causing leaflet apposition and hence valvular closure. The morphology of the valves was such that they were not considered to provide any significant impediment to the antegrade flow of lymph.     

Computer simulation of human mitral valve mechanics and motion

The human mitral valve is the left atrio-ventricular valve which is composed of several components including leaflets, chordae tendineae, papillary muscles, and the valve annulus. Any or all of these components may fail and contribute to various valvular diseases including mitral regurgitation and mitral valve prolapse. A computer simulation of mitral valve mechanics and motion was written in BASIC for micro-computers. This program allows valvular geometry and biomechanical parameters to be varied and records time varying motion of the valve and all components during systole including a graphic display of the valve leaflets.     

Anatomic study of the tricuspid valve in children

We performed an anatomic study of the right atrioventricular valve in children under one year of age using a conservative method of dissection of the heart valve. The main aspects studied were the number of cusps and their morphometric characteristics, such as the width of the base and the depth of the cusps. Other parameters studied were the number of papillary muscles, number of tendinous cords, and diameter of the fibrous ring and the last one were divided in three regions, anterior, posterior and septal for localization of cusps. Our results showed that the number of cusps varied from two to four. Three cusps was the commonest finding and the fourth cusp, if present, was classified as anterolateral in location. The anterior and septal cusps had bases bigger than those of the posterior and anterolateral cusps; the septal cusp was deeper than the others; and the number of tendinous cords was greater for the anterior and septal cusps than for the posterior and anterolateral cusps. In addition, the posterior region showed great variability: in 35.7% it was occupied by undeveloped valve tissue and the posterior valve in these cases was located anteriorly.