A study of the mechanical properties of ePTFE suture used as artificial mitral chordae.

BACKGROUND AND AIM OF THE STUDY: We investigated the dimensional and mechanical properties of polyetetrafluorene (ePTFE) sutures used as artificial chordae during mitral valve repair. METHODS: Mechanical properties of ePTFE synthetic chordae tendineae were tested with a servo hydraulic testing machine. Several different lengths from 2 to 14 cm were studied under both single and multiple mechanical traction. RESULTS: The mechanical behavior of artificial chordae reveals that three centimeters is the length over which we observe a significant increase in stiffness. The chordae stiffness grows further at the length greater than seven centimeters following a low number of traction cycles. CONCLUSION: The increase of the length of artificial ePTFE chordae is accompanied by an increasing stiffness that compromises the long-term resistance of the chordae. ePTFE length can alter the performance of artificial chordae. This suggests that mitral valve repairs which anchor ePTFE neochordae to the ventricular apex may have less durability than when anchored to the tips of the papillary muscles.

Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency.

Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attached chordae were used for histopathological and immunohistological assessment. Histologically, compared to normal controls (n = 3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture and increased thickness. Leaflet thickness was greater and chordae thickness lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa and atrialis; in FED, local thickening was predominant on the fibrosa side, with accumulation of proteoglycan-like material around the chordae. Collagen accumulation was observed in FED leaflets and chords and decreased in BD. Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but increased in FED leaflets and around chordae. Activated myofibroblasts accumulate in both diseased leaflets and chords, but more abundantly in FED chordae (P < 0.0001), independently of age, suggesting a role of these cells in chordal rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P < 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P < 0.01) indicating tissue remodeling. Upregulation of transforming growth factor beta and pERK signaling pathways was evident in both diseases but more prominent in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in control valves. Quantitative immunohistopathological analyses demonstrated distinct changes between BD and FED valves: predominant matrix degradation in BD and increased profibrotic signaling pathways in FED, indicating that BD and FED are 2 different entities. These results may pave the way for genetic studies of MVP and development of preventive drug therapies.

Clinical and pathological features of degenerative mitral valve disease: billowing mitral leaflet versus fibroelastic deficiency.

PURPOSE: Degenerative mitral valve disease is distinguished with billowing mitral leaflet (BML) or fibroelastic deficiency (FED). The purpose of this study is to evaluate the clinical characteristics and the pathohistological differences between BML and FED. METHODS: A total of 73 patients who diagnosed as degenerative mitral valve disease pathologically after mitral valve surgery for severe mitral regurgitation were enrolled. On the basis of echocardiographic features and gross appearances, they were classified as BML (9 cases) and FED (64 cases). RESULTS: In the BML group, multiple segments of the leaflet showed billowing with elongated chordae. Therefore excessive valve tissue needed to be removed by multiple resection and suture. The FED patients had focal myxomatous changes with ruptured chordae, a single resection and suture was frequently employed. In pathological examination, the valve thickness of the BML was nearly twice as thick as the FED, and the mucopolysaccharide accumulation of the Spongiosa in the BML was over 50%, while 30% in the FED. CONCLUSION: BML presents the characteristic valve thickening due to its abnormal production of mucopolysaccharide. Since excessive tissue was voluminous in the BML, high-grade plasty techniques, such as combination of multiple resection and chordal reconstruction were required.

Structural organization of collagen fibers in chordae tendineae as assessed by optical anisotropic properties and Fast Fourier transform.

The structural and supraorganizational arrangement of the chordae tendineae components is very important for a better understanding of their morphophysiological relationships. This study aims to evaluate the degree of statistical variability of the distribution and orientation of collagen fibers and their undulations (crimps), in porcine chordae tendineae. Polarization microscopy, in association with image analysis, was used for the analysis of birefringent images and detection of surface plots, Fast Fourier transforms, and form birefringence curve profiles. A marked variability in the collagen fiber's twisted and intertwined orientation was found not only along the long axis of the chordae tendineae but also in their 3-D structure, including that of the crimp structures. Crimp was demonstrated to not represent a homogeneous distribution of bands; the best methods to quantify its variability were the Fast Fourier transform and the line profile extended along the long axis of the chordae tendineae. Collagen fiber rings, considered to possibly protecting the integrity of the chordae tendineae, were observed to wrap around them. A statistically helical structure is assumed for the supraorganization of the collagen fibers in the chordae tendineae, which is suggested here to be a chiral body.

Elastic model for crimped collagen fibrils.

A physiologic constitutive expression is presented in algorithmic format for the nonlinear elastic response of wavy collagen fibrils found in soft connective tissues. The model is based on the observation that crimped fibrils in a fascicle have a three-dimensional structure at the micron scale that we approximate as a helical spring. The symmetry of this wave form allows the force/displacement relationship derived from Castigliano's theorem to be solved in closed form: all integrals become analytic. Model predictions are in good agreement with experimental observations for mitral-valve chordae tendinece.

Normal distribution of melanocytes in the mouse heart.

We report the consistent distribution of a population of pigmented trp-1-positive cells in several important septal and valvular structures of the normal mouse (C57BL/6) heart. The pigmented cell population was first apparent by E16.5 p.c. in the right atrial wall and extended into the atrium along the interatrial septum. By E17.5, these cells were found along the apical membranous interventricular septum near or below the surface of the endocardium. The most striking distribution of dark pigmented cells was found in the tricuspid and mitral valvular leaflets and chordae tendineae. The normal distribution of pigmented cells in the valvuloseptal apparatus of C57BL/6 adult heart suggests that a premelanocytic lineage may participate in the earlier morphogenesis of the valve leaflets and chordae tendineae. The origin of the premelanocyte lineage is currently unknown. The most likely candidate populations include the neural crest and the epicardially derived cells. The only cell type in the heart previously shown to form melanocytes is the neural crest. The presence of neural crest cells, but not melanocytes, in some of the regions we describe has been reported by others. However, previous reports have not shown a contribution of melanocytes or neural crest derivatives to the atrioventricular valve leaflets or chordae tendineae in mouse hearts. If these cells are of neural crest origin, it would suggest a possibly greater contribution and persistence of neural crest cells to the valvuloseptal apparatus than has been previously understood.

Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading.

This study was designed to identify the specific proteoglycans and glycosaminoglycans (GAGs) in the leaflets and chordae of the mitral valve and to interpret their presence in relation to the tensile and compressive loads borne by these tissues. Leaflets and chordae from normal human mitral valves (n = 31, obtained at autopsy) were weighed and selected portions digested using proteinase K, hyaluronidase, and chondroitinases. After fluorescent derivatization, fluorophore-assisted carbohydrate electrophoresis was used to separate and quantify the derivatized saccharides specific for each GAG type. In addition, the lengths of the chondroitin/dermatan sulfate chains were determined. Proteoglycans were identified by western blotting. The regions of the valve that experience tension, such as the chordae and the central portion of the anterior leaflet, contained less water, less hyaluronan, and mainly iduronate and 4-sulfated N-acetylgalactosamine with chain lengths of 50-70 disaccharides. These GAGs are likely associated with the small proteoglycans decorin and biglycan, which were found in abundance in the tensile regions. The valve regions that experience compression, such as the posterior leaflet and the free edge of the anterior leaflet, contained significantly more water, hyaluronan, and glucuronate and 6-sulfated N-acetylgalactosamine with chain lengths of 80-90 disaccharides. These GAGs are likely components of water-binding versican aggregates, which were abundant in the compressive loading regions. The relative amounts and distributions of these GAGs are therefore consistent with the tensile and compressive loads that these tissues bear. Finally, the concentrations of total GAGs and many different chondroitin/dermatan sulfate subclasses were significantly decreased with advancing age.

Immunolocalization of elastin, collagen type I and type III, fibronectin, and vitronectin in extracellular matrix components of normal and myxomatous mitral heart valve chordae tendineae.

The identification, distribution, and localization of matrix proteins and the proteins associated with normal and degenerated elastic fibers and collagen fibrils of myxomatous chordae tendineae were studied with immunoelectron microscopy. Ultrathin sections of L R White-embedded tissue were processed by indirect immunogold cytochemistry using primary antibodies against human alpha elastin, collagen types I and III, fibronectin, and vitronectin. In normal chordae tendineae, alpha elastin antibody heavily labeled the elastic fibers in spongiosa and fibrosa, but microfibrils around them were not labeled. Antibodies to collagen type I, collagen type III, and fibronectin all labeled the collagen fibers and microfibrils in the spongiosa. Fibronectin antibody labeling was higher than collagen type III, whereas labeling by anticollagen type I was lower. Intense labeling by vitronectin was observed on the microfibrils in the spongiosa and on electron-dense material around elastic fibers in the spongiosa and fibrosa. In myxomatous chordae tendineae, alpha elastin antibody heavily labeled degenerated elastic fibers, previously unidentified reticulated structures, and other moderately electron-dense material, both in the spongiosa and in the fibrosa, but not the electron-dense fibrous material around them. Antibodies to collagen types I, III, and fibronectin heavy labeled electron-dense aggregates of fibrous material. Vitronectin labeling was observed on electron-dense longitudinally running microfibrils and on the electron-dense microfibrils around degenerated elastic fibers.

Heat-induced changes in the mechanics of a collagenous tissue: isothermal free shrinkage.

We present data from isothermal free-shrinkage tests (i.e., performed in the absence of mechanical loads) wherein bovine chordae tendineae were subjected to temperatures from 65 to 85 degrees C for 120 to 1200 s. These data reveal four new insights into heat-induced denaturation of a collagenous tissue. First, a characteristic time for the free shrinkage appears to exhibit an Arrhenius-type relationship with temperature. Second, scaling the actual heating time via the characteristic time results in a single correlation between free shrinkage and the duration of heating; this correlation suggests a time-temperature equivalence. Third, it is the cumulative, not current, heating time that governs the free shrinkage. And fourth, heat-induced free shrinkage is partially recovered when the tissue is returned to 37 degrees C, this recovery also being time-dependent. Although these findings will help guide future experimentation and constitutive modeling, as well as the design of new heat-based clinical therapies, there is a pressing need to collect additional isothermal data, particularly in the presence of well-defined mechanical loads.