Biomedical subjects

Ivan Vesely

Publications and source records attributed to Ivan Vesely.

At least 19 recordsLinked to original sources

PubMed2006

Skewness angle of interfibrillar proteoglycans increases with applied load on mitral valve chordae tendineae.

In highly aligned connective tissues, such as tendon, collagen fibrils are linked together by proteoglycans (PGs). Recent mechanical and theoretical studies on tendon micromechanics have implied that PGs mediate mechanical interactions between adjacent collagen fibrils. We used transmission electron microscopy to observe the collagen fibril-PG interactions in porcine mitral valve chordae under variable loading conditions and found that PGs attached to collagen fibrils perpendicularly in the load-free situation, and became skewed when the chordae were loaded. The average skewness angle of PGs increased with the applied load, and hence the strain in the chordae. The observation of PG skewing with the application of load demonstrates that, in mitral valve chordae, interfibrillar slippage occurs and that PGs play a role in fibril-to-fibril interaction and likely transfer force. The results of this study provide new insights into the mechanical role of PGs and support some recent theoretical models.

Animals↗

PubMed2006

Novel geometries for tissue-engineered tendonous collagen constructs.

A promising approach to addressing the performance limitations of currently available mechanical and bioprosthetic heart valves lies in tissue engineering. Tissue-engineered valves should incorporate the complex microstructure of the native valves to mimic their unique mechanics. This would include a layered topology, mesh networks, and branched collagen fiber bundles. Our approach to heart valve tissue engineering is to develop the functional components of the aortic valve cusps separately in vitro and, once they are mature, integrate them into a composite valve structure. Here we report on our efforts to create more complex collagenous structures, suitable for heart valve tissue engineering. Collagen fiber bundles were fabricated using the principle of directed collagen gel contraction, using neonatal rat aortic smooth muscle cells and acid-soluble type I rat-tail tendon collagen. The collagen gels were cast into rectangular or branched wells with porous end holders that constrained the gels longitudinally but allowed contraction to occur transverse to the long axis. Pairs of such constructs were placed in direct contact with each other and cultured further to determine whether they integrated to form continuous tissue. After 6-8 weeks of culture, highly compacted and aligned collagen fiber bundles formed. Mechanical testing revealed that linear constructs (2 free ends) with an 8:1 aspect ratio were significantly stronger than similar constructs with an aspect ratio of 2:1 (mean +/- SD, 298 +/- 90 kPa vs. 152 +/- 49 kPa; p < .001). Branching reduced mechanical strength considerably. Constructs fabricated with 4 free ends were significantly weaker than constructs with 3 ends (31 +/- 32 kPa vs. 116 +/- 66 kPa; p < .003). Histologic images demonstrated the integration of the crossed collagen bundles, with a bonding strength of 2.1 +/- 1.1 g (0.02 N). We found that the geometry of the molds into which the collagen constructs are cast can greatly affect their mechanical strength: multibranched constructs were the weakest, and long, linear constructs were the strongest. We also found that integration of collagen constructs occurs in vitro and that the fabrication of a composite structure in vitro is probably feasible.

Absorbable Implants↗

PubMed2005

Heart valve tissue engineering.

Tissue-engineered heart valves have been proposed by physicians and scientists alike to be the ultimate solution for treating valvular heart disease. Rather than replacing a diseased or defective native valve with a mechanical or animal tissue-derived artificial valve, a tissue-engineered valve would be a living organ, able to respond to growth and physiological forces in the same way that the native aortic valve does. Two main approaches have been attempted over the past 10 to 15 years: regeneration and repopulation. Regeneration involves the implantation of a resorbable matrix that is expected to remodel in vivo and yield a functional valve composed of the cells and connective tissue proteins of the patient. Repopulation involves implanting a whole porcine aortic valve that has been previously cleaned of all pig cells, leaving an intact, mechanically sound connective tissue matrix. The cells of the patients are expected to repopulate and revitalize the acellular matrix, creating living tissue that already has the complex microstructure necessary for proper function and durability. Regrettably, neither of the 2 approaches has fared well in animal experiments, and the only clinical experience with tissue-engineered valves resulted in a number of early failures and patient death. This article reviews the technological details of the 2 main approaches, their rationale, their strengths and weaknesses, and the likely mechanisms for their failure. Alternative approaches to valvular tissue engineering, as well as the role of industry in shaping this field in the future, are also reviewed.

Animals↗

PubMed2005

Invariant formulation for dispersed transverse isotropy in aortic heart valves: an efficient means for modeling fiber splay.

Most soft tissues possess an oriented architecture of collagen fiber bundles, conferring both anisotropy and nonlinearity to their elastic behavior. Transverse isotropy has often been assumed for a subset of these tissues that have a single macroscopically-identifiable preferred fiber direction. Micro-structural studies, however, suggest that, in some tissues, collagen fibers are approximately normally distributed about a mean preferred fiber direction. Structural constitutive equations that account for this dispersion of fibers have been shown to capture the mechanical complexity of these tissues quite well. Such descriptions, however, are computationally cumbersome for two-dimensional (2D) fiber distributions, let alone for fully three-dimensional (3D) fiber populations. In this paper, we develop a new constitutive law for such tissues, based on a novel invariant theory for dispersed transverse isotropy. The invariant theory is derived from a novel closed-form 'splay invariant' that can easily handle 3D fiber populations, and that only requires a single parameter in the 2D case. The model fits biaxial data for aortic valve tissue as accurately as the standard structural model. Modification of the fiber stress-strain law requires no reformulation of the constitutive tangent matrix, making the model flexible for different types of soft tissues. Most importantly, the model is computationally expedient in a finite-element analysis, demonstrated by modeling a bioprosthetic heart valve.

Anisotropy↗

PubMed2005

Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements: an extracellular matrix and echocardiographic study.

OBJECTIVES: This study assessed apparently normal mitral valves from patients with congestive heart failure (CHF) using biochemical and echocardiographic measures of extracellular matrix (ECM) and anatomy. BACKGROUND: Mitral regurgitation (MR) is frequently found in patients with CHF. This MR is considered purely functional, yet animal studies suggest that altered left ventricular (LV) function leads to increased cellularity and fibrosis of the mitral valve. Therefore, we hypothesized that patients with CHF might have partly organic MR, via dysfunctional valvular remodeling. METHODS: Mitral valves from transplant recipient hearts of patients with CHF (23 dilated, 14 ischemic) were analyzed for deoxyribonucleic acid (DNA), collagen, glycosaminoglycan (GAG), and water concentrations and compared with autopsy controls. Cardiac dimensions and functional parameters (measured from recent echocardiograms) were compared with biochemical parameters using a repeated measures generalized linear model. RESULTS: The mitral valves in CHF had up to 78% more DNA (p <0.03), 59% more GAGs (p <0.02), and 15% more collagen (p <0.007), but 7% less water (p <0.05) than normal. The absence of anterior leaflet redundancy was associated with these deranged biochemical measures (p <0.03). Associations were found between leaflet thickness and DNA concentration (+, p=0.003), annular diameter and chordal collagen (+, p=0.03), and water concentration and both left atrial diameter (-, p=0.008) and LV collagen concentration (-, p=0.04). CONCLUSIONS: Mitral valves in CHF are biochemically different from normal, with ECM changes that are influenced by the altered cardiac dimensions. This remodeling suggests that MR in patients with CHF may not be purely functional, and that these valves are not "normal."

Adult↗

PubMed2005

Inverse parameter fitting of biological tissues: a response surface approach.

In this paper, we present the application of a semi-global inverse method for determining material parameters of biological tissues. The approach is based on the successive response surface method, and is illustrated by fitting constitutive parameters to two nonlinear anisotropic constitutive equations, one for aortic sinus and aortic wall, the other for aortic valve tissue. Material test data for the aortic sinus consisted of two independent orthogonal uniaxial tests. Material test data for the aortic valve was obtained from a dynamic inflation test. In each case, a numerical simulation of the experiment was performed and predictions were compared to the real data. For the uniaxial test simulation, the experimental targets were force at a measured displacement. For the inflation test, the experimental targets were the three-dimensional coordinates of material markers at a given pressure. For both sets of tissues, predictions with converged parameters showed excellent agreement with the data, and we found that the method was able to consistently identify model parameters. We believe the method will find wide application in biomedical material characterization and in diagnostic imaging.

Algorithms↗

PubMed2005

Mitral valve stiffening in end-stage heart failure: evidence of an organic contribution to functional mitral regurgitation.

OBJECTIVE: Mitral regurgitation is a complication for many patients with congestive heart failure. Although this regurgitation is considered purely functional, we hypothesize that the alterations in cardiac geometry and function induce dysfunctional remodeling of the mitral valve, which can be demonstrated by alterations in the material behavior of the leaflets and chordae. METHODS: Mitral leaflets and chordae from 23 valves from transplant recipient hearts (11 with dilated and 12 with ischemic cardiomyopathy) and from 21 normal valves (from autopsy) were mechanically tested. RESULTS: Radially oriented anterior mitral leaflet strips from failing hearts were 61% stiffer and 23% less viscous on average than those from autopsy control hearts. The mean stiffness of circumferentially oriented anterior leaflet strips was 50% higher than that of control hearts. Leaflet extensibility was reduced 35% overall. Likewise, the failing heart chordae were an average of 16% stiffer (all P < or = .05). CONCLUSIONS: Mitral valves in congestive heart failure have significantly altered mechanics that suggest that the tissue is permanently distended and fibrotic and might be unable to stretch sufficiently to cover the valve orifice. These material changes in the valve tissues accompany the biochemical alterations in extracellular matrix composition that we have previously reported. Our finding of leaflet and chordal remodeling suggests that mitral regurgitation in patients experiencing heart failure might not be purely functional and that these mitral valves should not be considered normal. Moreover, there are implications for strategies of mitral valve surgery or percutaneous approaches in this patient population.

Chordae Tendineae↗

PubMed2005

Fractional order viscoelasticity of the aortic valve cusp: an alternative to quasilinear viscoelasticity.

BACKGROUND: Quasilinear viscoelasticity (QLV) theory has been widely and successfully used to describe the time-dependent response of connective tissues. Difficulties remain, however, particularly in material parameter estimation and sensitivities. In this study, we introduce a new alternative: the fractional order viscoelasticity (FOV) theory, which uses a fractional order integral to describe the relaxation response. FOV implies a fractal-like tissue structure, reflecting the hierarchical arrangement of collagenous tissues. METHOD OF APPROACH: A one-dimensional (I-D) FOV reduced relaxation function was developed, replacing the QLV "box-spectrum" function with a fractional relaxation function. A direct-fit, global optimization method was used to estimate material parameters from stress relaxation tests on aortic valve tissue. RESULTS: We found that for the aortic heart valve, FOV had similar accuracy and better parameter sensitivity than QLV, particularly for the long time constant (tau2). The mean (n = 5) fractional order was 0.29, indicating that the viscoelastic response of the tissue was strongly fractal-like. RESULTS SUMMARY: mean QLV parameters were C = 0.079, tau1 = 0.004, tau2 = 76, and mean FOV parameters were beta = 0.29, tau = 0.076, and rho = 1.84. CONCLUSIONS: FOV can provide valuable new insights into tissue viscoelastic behavior Determining the fractional order can provide a new and sensitive quantitative measure for tissue comparison.

Animals↗

PubMed2005

Mesostructures of the aortic valve.

BACKGROUND AND AIM OF THE STUDY: The aortic valve cusp is commonly described as a three-layered structure containing circumferentially aligned fiber bundles. Little is known, however, regarding fiber bundle sizes, branching patterns, or how they are connected. This is because previous morphological studies relied primarily on histological sectioning and staining techniques, which tend to affect all of the collagen, regardless of structure or orientation. METHODS: To address this problem, a novel system was developed for the visualization and analysis of the intermediate-scale 'mesostructures' of aortic valve cusps. Mesostructures are defined as the branching fiber bundle and membrane structures that make up the valve. This system uses elliptically polarized light to provide contrast between collagen mesostructures without the need for embedding, staining, or other contrast-enhancing techniques. Using this system, high-resolution images of 42 whole porcine aortic valve cusps were acquired in an unloaded (i.e. resting) condition and during application of controlled manipulation. Image-processing algorithms were developed to quantify fiber bundle morphological features and produce detailed maps of the fiber bundle patterns. RESULTS: Fiber bundle sizes and patterns were found to be significantly different for each of the three cusps. The non-coronary cusp had a significantly smaller bundle diameter (0.9 +/- 0.07 mm) than the left and right coronary cusps (1.1 +/- 0.08 mm). The left and non-coronary cusps appeared to be mirror images of each other, whereas the right coronary cusp was self-symmetric. When applying controlled loads to the cusp specimens, thin, overlapping, collagenous membranes were often found which connected the fiber bundles. Interesting pinnate fiber branching patterns were also found. CONCLUSION: These morphological results were strikingly different than the currently accepted three-layer description, and may provide valuable insight into aortic valve structure-function relationships.

Animals↗

PubMed2004

Characterization of statically loaded tissue-engineered mitral valve chordae tendineae.

Chordae tendineae are essential to the proper function of the mitral valve. Native chordae contain a dense collagenous core and an outer elastin sheath. We have been using the principle of directed collagen gel shrinkage to fabricate tissue-engineered mitral valve chordae. Because the microstructure of biologic tissues determines their mechanical behavior, the morphology of collagen and elastin in tissue-engineered chordae should mimic that of native chordae. The objective of this study, therefore, was to examine the morphology of our tissue-engineered constructs in comparison to native chordae. A collagen-cell suspension was cast into silicon rubber wells with microporous anchors at the ends and cultured in an incubator. The anchors allowed shrinkage to occur only transverse to the long axis of the wells, thus creating highly aligned collagen fibril constructs. The collagen constructs were cultured for 8 weeks and characterized mechanically, histologically, and biochemically at different culture time points. Histologic sections showed that in all mature constructs collagen fibers were oriented parallel to the long axis of the constructs. At the edge of the tissue collagen fibers were in general straight, whereas in the middle of the tissue they were wavy. Transmission electron microscopy showed a progressive increase in the density and longitudinal orientation of collagen fibrils with culture time. Light and scanning electron microscopy showed the presence of an elastin sheath around the collagen core. Immunostaining demonstrated that smooth muscle cells differentiate during tissue development and TUNEL assay showed that cells in the interior of the constructs undergo apoptosis. This study has demonstrated that collagen-cell constructs, with material properties and microstructure similar to native mitral valve chordae, can be developed using static culture.

Animals↗

PubMed2004

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.

Acetylgalactosamine↗

PubMed2004

Biomechanical and echocardiographic characterization of flail mitral leaflet due to myxomatous disease: further evidence for early surgical intervention.

BACKGROUND: Flail mitral leaflet (FML) is a common complication of mitral valve prolapse, often leading to severe mitral regurgitation (MR) and left ventricular dysfunction. In the absence of timely surgical correction, survival is significantly impaired. Early recognition of FML and identification of risk factors is important because early intervention increases the chances of survival. METHODS: We studied 123 patients undergoing mitral valve surgery for severe MR caused by myxomatous disease. Chart review, echocardiography, and tensile testing were performed. RESULTS: Thirty-eight patients had FML, and 85 patients had non-flail mitral leaflet (non-FML). Patients with FML were younger (53.7 +/- 1.8 vs 59.3 +/- 1.4 years, P =.02), had more severe MR (3.89 +/- 0.04 vs 3.76 +/- 0.04, P =.02), were less likely to be in New York Heart Association class III or IV heart failure (5% vs 20%, P =.037), and were less likely to have bileaflet mitral valve prolapse (5% vs 38%, P <.001) than non-FML patients. Valve tissue from patients with FML had less stiff chordae (23.5 +/- 3.6 vs 59.1 +/- 11.7 Mpa, P =.006) that tended to have a lower failure stress (3.8 +/- 0.9 vs 9.6 +/- 2.2 Mpa, P =.07) and had more extensible leaflets (56.4% +/- 7.9% vs 42.9% +/- 2.7% strain, P =.04) compared with that of non-FML patients. CONCLUSIONS: The development of FML may result from intrinsic tissue abnormalities and is associated with a distinct subset of the myxomatous population. Identification of such clinical characteristics in this population and knowledge of an implicit mechanical abnormality of valve tissue may further the argument for early surgical correction.

Chordae Tendineae↗

PubMed2004

The effect of strain rate on the viscoelastic response of aortic valve tissue: a direct-fit approach.

Knowledge of strain-rate sensitivity of soft tissue viscoelastic and nonlinear elastic properties is important for accurate predictions of biomechanical behavior and for quantitative assessment of the effects of disease or surgical/pharmaceutical intervention. Soft tissues are known to exhibit mild rate sensitivity, but experimental artifacts related to testing system control can confound estimation of these effects. "Perfect" ramp-and-hold stress-relaxation tests become difficult at high strain rates because of problems related to undershoot/overshoot error and vibrations. These errors can introduce unwanted bias into parameter estimation methods that rely on idealizations of the applied ramp-and-hold displacement. To address these problems, we describe a new method for estimating quasilinear viscoelastic (QLV) parameters that directly fits the QLV constitutive model to the actual point-wise stress-time history of the test, using an adaptive grid refinement (AGR) global optimization algorithm. This new method significantly improves the accuracy and predictivity of QLV parameter estimates for heart valve tissues, compared to traditional methods that use idealized displacement data. We estimated QLV parameters for aortic valve tissue over a range of physiologic displacement rates, finding that the viscoelastic content parameter (C) increased slightly with increasing strain rate, but the fast (tau1) and slow (tau2) time constants were strain rate insensitive.

Algorithms↗

PubMed2004

Stress relaxation preconditioning of porcine aortic valves.

In uniaxial tensile testing, load preconditioning is used to generate repeatable load/elongation curves and set a "reference state" for subsequent tensile tests. We have observed however, that for porcine aortic valve (PAV) tissues, preconditioning does not lead to repeatable stress relaxation curves. We thus investigated possible experimental protocols that could be used to generate repeatable load/elongation and stress relaxation curves. To quantify repeatability of stress relaxation, we compared normalized loads at the same time points from repeated stress relaxation curves and computed a repeatability ratio. We found that PAV specimens can generate repeatable stress relaxation curves (repeatability ratio >0.95) if they are subjected to at least five cycles of repeated load preconditioning and stress relaxation. We also found that a single cycle of loading/unloading prior to each stress relaxation phase is sufficient to generate repeatable stress relaxation curves. Stress relaxation preconditioning is therefore required to generate repeatable load/elongation and stress relaxation curves. It is expected that such curves will generate more accurate material constants for the characterization and modeling of PAV mechanics.

Animals↗

PubMed2004

Relationship between collagen fibrils, glycosaminoglycans, and stress relaxation in mitral valve chordae tendineae.

The tensile properties of mitral valve chordae tendineae derive from their structural make-up. The objectives of this study were to compare the stress relaxation properties of different types of chordae and relate their variation to structural features. Fifty chordae from eight hearts were subjected to stress relaxation tests. The percent stress relaxation and the relaxation rates were found to increase in the order of marginal. basal, and strut chordae. The water content of the three types of chordae was the same (marginal 77.1+/-5.9%, basal 77.0+/-3.4%, strut 78.0+/-2.3% wet weight). The collagen, elastin, and glycosaminoglycan (GAG) content in chordae were quantified using hydroxyproline assay, fastin elastin assay, and fluorophore-assisted carbohydrate electrophoresis, respectively. Collagen content of marginal chordae was only slightly less than that of basal and strut chordae (marginal 56.6+/-8.2%, basal 61.4+/-5.6%, strut 63.8+/-3.9% dry weight). There was also no significant difference in elastin content between the chordae (marginal 5.3+/-3.2%, basal 5.4+/-2.7%, strut 4.6+/-1.7% dry weight). However, the concentrations of unsulfated chondroitin/dermatan sulfate, 6-sulfated chondroitin sulfate, and 4-sulfate chondroitin sulfate significantly decreased in the order of marginal, basal, and strut. The total GAG-content also decreased in the order of marginal, basal, and strut (p = 0.06). The greater amount of GAGs in marginal versus strut chordae is consistent with our previous observations that marginal chordae have a greater collagen fibril density and thus more GAG-mediated, fibril-to-fibril linkages. The greater number of proteoglycan linkages may prevent the slippage of fibrils with respect to each other, and thus reduce stress relaxation. The different viscoelastic properties of mitral valve chordae can thus be explained morphologically.

Chordae Tendineae↗

PubMed2004

Cell viability mapping within long-term heart valve organ cultures.

BACKGROUND AND AIM OF THE STUDY: Organ cultures maintain cells within their native microstructural environment, and thus offer greater potential for studying tissue disease and remodeling than do monolayer cell cultures or pathological examinations of diseased tissue. To validate an in-vitro heart valve organ culture model, cell viability was examined within valve tissues over sustained culture periods. METHODS: Following culture of blocks of valve tissue for 1 to 49 days, cross-sections were cut with a vibratome, stained with a LIVE/DEAD kit, and imaged with confocal microscopy to quantify the number of live and dead cells present. RESULTS: In numerous organ cultures, valvular interstitial cells were found to be viable beyond 30 days. Live cells were abundant in the central region of the valve, but more sparse in the deepest central regions. Dead cells were found mainly on the surface of both fresh tissues and tissues after prolonged culture, with few dead cells occurring centrally. CONCLUSION: This is the first reported mapping of cell viability within heart valve organ cultures, and results suggest that extended organ culture of valve leaflets is indeed possible. The derived viability staining methods have wide applicability for organ cultures of other tissues as well as tissue-engineered matrices.

Animals↗

PubMed2003

Ultraviolet light-induced modification of crosslinked hyaluronan gels.

Hyaluronan (HA) gels (hylans) crosslinked with divinyl sulfone (DVS) are highly biocompatible and can be structurally modified to obtain desired mechanical properties that are attractive for their use as tissue-engineering scaffolds. However, unmodified hylan gels are not good substrates for cell attachment or infiltration, likely as a result of their smooth surface and the highly anionic nature of HA. This study investigated whether the cell-adhering characteristics of hylan gels could be enhanced by irradiation with ultraviolet (UV) light, with or without prior dehydration. The attachment and proliferation of neonatal rat smooth muscle cells atop these gels was compared with that on unmodified (control; C) or dehydrated (D) gels. UV-induced changes to gel structure and chemistry were characterized by confocal and electron microscopy, and fluorphore-assisted carbohydrate electrophoresis (FACE). Cell attachment was sparse on both unmodified (C) and dehydrated (D) gels. Significantly higher levels of cell attachment were observed on the surface of irradiated (UV) and dehydrated-irradiated (DUV) gels, likely because of texturing of the gel surface by UV light. In addition, dehydration of gels before UV irradiation created irregular pore-like structures through which cells appeared to migrate into the interior. FACE assays demonstrated that UV-irradiation alters the chemistry of HA, causing limited breakdown of HA chains and DVS crosslinks within gel and possibly creating new crosslinks that have not yet been identified. Because the hylan gels are altered structurally and chemically, binding of cells to the material is likely to be more permanent than possible by other approaches, such as coating of cell-adhesive matrix factors on the gel surface, described previously. The significance of this work is that we have developed a technique for the modification of DVS-crosslinked HA (hylans) to enhance their performance as a cellular scaffold for tissue-engineering applications.

Animals↗

PubMed2003

Glycosaminoglycan profiles of myxomatous mitral leaflets and chordae parallel the severity of mechanical alterations.

OBJECTIVES: This biochemical study compared the extracellular matrix of normal mitral valves and myxomatous mitral valves with either unileaflet prolapse (ULP) or bileaflet prolapse (BLP). BACKGROUND: Myxomatous mitral valves are weaker and more extensible than normal valves, and myxomatous chordae are more mechanically compromised than leaflets. Despite histological evidence that glycosaminoglycans (GAGs) accumulate in myxomatous valves, previous biochemical analyses have not adequately examined the different GAG classes. METHODS: Leaflets and chordae from myxomatous valves (n = 41 ULP, 31 BLP) and normal valves (n = 27) were dried, dissolved, and assayed for deoxyribonucleic acid, collagen, and total GAGs. Specific GAG classes were analyzed with selective enzyme digestions and fluorophore-assisted carbohydrate electrophoresis. RESULTS: Biochemical changes were more pronounced in chordae than in leaflets. Myxomatous leaflets and chordae had 3% to 9% more water content and 30% to 150% higher GAG concentrations than normal. Collagen concentration was slightly elevated in the myxomatous valves. Chordae from ULP had 62% more GAGs than those from BLP, primarily from elevated levels of hyaluronan and chondroitin-6-sulfate. CONCLUSIONS: The GAG classes elevated in the myxomatous chordae are associated with matrix microstructure and elastic fiber deficiencies and may influence the hydration-related "floppy" nature of these tissues. These abnormalities may be related to the reported mechanical weakness of myxomatous chordae. The biochemical differences between ULP and BLP confirm previous mechanical and echocardiographic distinctions.

Adult↗