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Biomedical subjects

Ivan Vesely

Publications and source records attributed to Ivan Vesely.

30 records · Page 2Linked to original sources
PubMed2003

Loss of chondroitin 6-sulfate and hyaluronan from failed porcine bioprosthetic valves.

Explanted porcine bioprosthetic valves have a thinned spongiosa, partially because of an overall loss of glycosaminoglycans (GAGs). We measured the concentrations of specific GAG classes in explanted bioprosthetic valves (n = 14, implanted 12.0 +/- 4.7 years) compared with glutaraldehyde-fixed porcine controls. After extraction with NaOH, GAGs were analyzed using either a hexuronic acid assay or fluorophore-assisted carbohydrate electrophoresis to quantify the individual GAG classes. The total GAG concentration in explants was 198 +/- 95 pmol/mg wet weight-93% less than freshly fixed controls. Explants also contained altered proportions of the different GAG classes relative to controls. The proportions of hyaluronan and chondroitin/dermatan-6-sulfate were reduced from 39 to 7% and 34 to 18% of total GAGs, respectively. The predominant explant GAG class was chondroitin/dermatan-4-sulfate (proportion elevated from 14 to 70%). This GAG is commonly found in the collagen-associated proteoglycan decorin, which is likely well crosslinked by glutaraldehyde. Chondroitin-6-sulfate is commonly found in the water- and hyaluronan-binding proteoglycan versican, which is likely poorly crosslinked. The loss of versican and its associated water-binding capacity is consistent with the thinned spongiosa. The resultant compromise of hydration, compressive resistance, and viscoelasticity may be responsible for the deterioration of the bioprosthesis in vivo.

Animals↗
PubMed2003

A new method of estimating gauge length for porcine aortic valve test specimens.

Porcine aortic valve (PAV) cusps are folded and wrinkled in the in vitro state. In the tensile testing of PAV specimens, estimating gauge length (the length at which a specimen starts to offer measurable resistance to load) is often difficult and subjective. We have therefore developed a new method for estimating the gauge length of such tissues. The method is based on the observation that the specimen's gauge length can be associated with a stationary point on the slope of its load-length curve if loaded from a wrinkled state, or a state of slight compression. We represented the load-length response of test specimens in the low-load, high-compliance region by a cubic function and determined the stationary point on the slope of the function using elementary calculus. The cubic function representation is fine-tuned by reducing or expanding an originally selected "test region" until the correlation coefficient of the cubic fit is maximized. The new method was applied to data obtained from the tensile testing of strips of heart valve tissue and was found to be objective, repeatable and robust.

Animals↗
PubMed2003

A structural basis for the size-related mechanical properties of mitral valve chordae tendineae.

It has been reported previously that the mechanical properties of mitral valve chordae tendineae vary with chordal size and type. The popularity of mitral valve repair and chordal transposition warrant a better understanding of this phenomenon. The objectives of this study were to characterize the size- and type-related variations in chordal mechanics and explain them from the ultra-structural viewpoint. A total of 52 porcine mitral valve chordae from eight hearts were mechanically tested. We found that thicker chordae were more extensible than thinner chordae (4.2+/-1.5%, 8.1+/-2.5%, 15.7+/-3.9% and 18.4+/-2.8% strain corresponding to chordae with cross-sectional areas of 0.1-0.5, 0.5-1.0, 1.0-2.0, and 2.0-3.0mm(2), respectively), and had lower moduli (90.1+/-22.3, 83.7+/-18.5, 66.3+/-13.5 and 61.7+/-13.3 MPa corresponding to the same chordae groups). Polarized light microscopy was used to measure collagen fibril crimp. Thicker chordae had smaller crimp period than thinner chordae (11.3+/-1.4 microm vs. 14.8+/-3.0 microm), and were thus more highly crimped. Thicker chordae could therefore extend to greater strain before lock-up. Transmission electron microscopy (TEM) was used to measure choral fibril ultra-structure. Thinner chordae had lower average fibril diameter than thicker chordae but greater average fibril density. The cross-sectional area occupied by fibrils, however, was found to be constant at 49+/-2% regardless of chordal size or type. The difference in moduli between thick and thin chordae can therefore be explained by differences in fibril packaging and hence fibril-to-fibril interactions. According to a simple fibril interaction model, chordae with smaller diameter fibrils will have a greater number of fibril-to-fibril interactions, and hence a greater modulus.

Anatomy, Cross-Sectional↗
PubMed2003

Fabrication of mitral valve chordae by directed collagen gel shrinkage.

The principles of tissue engineering are being used to explore numerous applications in reconstructive surgery. Mitral valve chordae are one such potential area, as mitral valve repair is increasing in popularity and synthetic materials have not been used widely. The use of cells, combined with reconstituted type I collagen, is an attractive option for fabricating materials for the replacement of thin tendonous structures such as mitral valve chordae. We have been using the principle of directed collagen gel shrinkage to fabricate tendinous structures with good mechanical properties. In this study, our objective was to maximize the strength of the collagen constructs by choosing cell type and optimizing cell-seeding density, culture time, and initial collagen concentration. A collagen-cell suspension was cast into silicone 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 collagenous constructs. Collagen gel contraction increased with higher cell-seeding density. The optimal value was 10(6) cells/mL. The rate of gel contraction decreased with the initial collagen concentration. Fibril density increased with culture time, as the gel contracted. After the system was optimized, the mechanical strength of the constructs increased to 1.1 MPa, a value at least an order of magnitude greater than previously published results with similar systems. This study has demonstrated that collagen-cell constructs, with material properties similar to those of native mitral valve chordae, can be developed using the principle of directed collagen gel shrinkage. These structures may have application in other areas that require small-diameter tendons.

Animals↗
PubMed2003

3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro.

Recent findings have implicated the 5-hydroxytryptamine 2B (5-HT2B) serotonin receptor in mediating the heart valve fibroplasia [valvular heart disease (VHD)] and primary pulmonary hypertension observed in patients taking the now-banned appetite suppressant fenfluramine (Pondimin, Redux). Via large-scale, random screening of a portion of the receptorome, we have discovered that the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") and its N-demethylated metabolite 3,4-methylenedioxyamphetamine (MDA) each preferentially bind to and activate human recombinant 5-HT2B receptors. We also demonstrate that MDMA and MDA, like fenfluramine and its N-deethylated metabolite norfenfluramine, elicit prolonged mitogenic responses in human valvular interstitial cells via activation of 5-HT2B receptors. We also report that pergolide and dihydroergotamine, two drugs recently demonstrated to induce VHD in humans, potently activate 5-HT2B receptors, thus validating this assay system for its ability to predict medications that might induce VHD. Our discovery that MDMA and a major metabolite, MDA, induce prolonged mitogenic responses in vitro similar to those induced by fenfluramine and norfenfluramine in vivo (i.e., valvular interstitial cell fibroplasia) predict that long-term MDMA use could lead to the development of fenfluramine-like VHD. Because of the widespread abuse of MDMA, these findings have major public health implications. These findings also underscore the necessity of screening current and future drugs at h5-HT2B receptors for agonist actions before their use in humans.

3,4-Methylenedioxyamphetamine↗
PubMed2002

Clinical, echocardiographic, and biomechanical differences in mitral valve prolapse affecting one or both leaflets.

Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation necessitating surgical correction. Unileaflet prolapse (ULP), usually involving the posterior leaflet, is more common than bileaflet prolapse (BLP), which is more difficult to repair. Little is known about clinical, echocardiographic, and biomechanical differences between ULP and BLP. In this study, biomechanical testing was performed on mitral valve leaflets and chordae obtained at operation for severe mitral regurgitation. Preoperative clinical characteristics and echocardiographic measurements were obtained on surgical patients (ULP = 88, BLP = 37). Men outnumbered women by a factor of 4:1 in ULP, and by 3:1 in BLP. Patients with BLP were younger (53.2 +/- 1.7 vs 59.5 +/- 1.1 years) than those with ULP, and this difference was greater in women (48.9 +/- 2.5 vs 62.9 +/- 2.2 years). BLP patients were less likely to be hypertensive, and more likely to undergo valve replacement rather than repair. Echocardiography showed that BLP leaflets were longer and thicker than ULP leaflets. The severity of mitral regurgitation was similar in both groups, although ULP patients had a much higher incidence of flail leaflets (45% vs 5% in BLP). Mechanical strength of chordae was greater in BLP than in ULP, although leaflet strength was similar. The increased chordal strength in BLP may be responsible for less flail. In patients with MVP and severe mitral regurgitation requiring surgery, ULP and BLP are distinct entities with substantial differences in the population affected, in echocardiographic manifestations including prevalence of flail, in chordal mechanics, and in the likelihood of surgical repair.

Biomechanical Phenomena↗
PubMed2002

Smooth muscle cell adhesion on crosslinked hyaluronan gels.

Hyaluronic acid (HA)-based polymers (hylans) are highly biocompatible and can be structurally modified to obtain desired mechanical properties. This study evaluated divinyl sulfone-crosslinked solid and particulate hylans as cellular scaffolds. These two hylan types differ in surface characteristics, mode of preparation, HA content, and extent of crosslinking. Neonatal rat aortic smooth muscle cells were cultured on hylan gels coated with matrix factors including collagen I, ECM gel, laminin, and fibronectin and on uncoated controls for < or =4 weeks. Cell attachment was sparse on uncoated controls but significantly enhanced on coated gels. Cell morphology was influenced by the identity of the matrix factors coated and the surface topography of the hylan gels. Cells attached to coated particulate gels appeared either highly spread (collagen, fibronectin) or irregularly shaped (ECM gel, laminin). Cells on laminin and fibronectin-coated solid gels were rounded and nonproliferative. Cells proliferated most rapidly on ECM gel-coated gels. The uneven surface of particulate gels induced more protein deposition and the subsequent attachment and active proliferation of cells. This study shows that surface texturizing and subsequent surface treatment with matrix factors enhances cell attachment and proliferation of hylans. These results are useful toward developing bioengineered materials based on cell-hylan composites.

Animals↗
PubMed2002

Characteristics of compressive strains in porcine aortic valves cusps.

BACKGROUND AND AIM OF STUDY: Previous studies in our laboratory have revealed the presence of compressive strains at the base of the non-coronary (NC) cusp of porcine aortic valves. Since these strains have been shown to damage bioprosthetic valve tissue, the mechanism by which they are induced in valve tissues should be investigated. METHODS: Whole porcine aortic valves were pressurized and the induced strain patterns measured on aortic valve cusps and roots. Measurements were made before and after trimming of excess ventricular muscle and mitral valve tissue. RESULTS: Negative (compressive) radial strains were found only in the NC cusp. Trimming of surrounding muscle increased the magnitude of both the tensile circumferential strains and compressive radial strains in the NC cusp. The left and right coronary cusps (LC, RC respectively) had similar positive radial and circumferential strains, and trimming had inconsistent effects on the strain patterns. Trimming of the aortic root increased root strains adjacent to the NC cusp, thus increasing positive circumferential strains and negative radial strains in the NC cusp. Analysis of images obtained during loading indicated that a wrinkle formed at the base of the NC cusp in 66% of cases in which negative strains were observed. CONCLUSION: Negative radial strains were induced in the NC cusp as it stretched circumferentially during static pressurization. In many valves, negative strains resulted from radial folding or wrinkling of the valve cusp. Since the RC and LC cusps had circumferential and radial strains that were not similar to those of the NC cusp, it is likely that the NC cusp has a different internal fibrous organization.

Animals↗
PubMed2002

Towards tissue engineering of a composite aortic valve.

A tissue-engineered valve needs to incorporate the complex microstructure of the native aortic valve if it is to be as durable as existing bioprosthetic valves. Native aortic valve cusps contain large collagen fiber bundles surrounded by tubes of elastin, linked together by elastin sheets and struts. They also contain glycosaminoglycans (GAGs) that bind water and give the valve cusp a gelatinous consistency. Our approach to tissue engineering the aortic valve is to fabricate the cusp from the building blocks described above. We have developed collagen fiber bundles using the principle of directed collagen gel shrinkage, a GAG matrix by crosslinking high molecular weight hyaluronan with divinyl sulfone, and elastin sheets and tubes by culturing neonatal aortic fibroblasts on the appropriate substrates. To make collagen fiber bundles, cells are mixed with solubilized fibrillar collagen and cast into silicon rubber wells fitted with microporous holders to entrap the gel and hold it in place. As the cells interact with the collagen fibrils, they contract and compact the gel. Since the gel is constrained in the longitudinal direction, it can contract only laterally, forming well-aligned, strong (> 1 MPa) collagen fiber bundles. Elastin sheaths from naturally around the collagen fiber bundles and atop the hyaluronan gel when the neonatal aortic fibroblasts are cultured for more than 4 weeks. The individual building blocks of the aortic valve cusp, designed and fabricated according to patterns dictated by the microstructure of the native aortic valve, will be stacked together to make the final composite, tissue-engineered aortic valve cusp.

Absorbable Implants↗
PubMed2002

Failure mechanics of mitral valve chordae tendineae.

BACKGROUND AND AIM OF THE STUDY: Rupture of chordae tendineae is the main cause of mitral valve insufficiency, and often requires corrective surgery. The precise mechanisms of chordal rupture, however, are unknown. METHODS: Failure mechanics were measured in porcine mitral valve chordae (37 anterior marginal, 40 anterior basal, 35 posterior marginal, and 38 posterior basal). Full-length chordae were weighed, measured, and stretched to failure in an Instron tensile testing machine. The ruptured ends were characterized under a dissecting microscope. RESULTS: Marginal chordae had 68% thinner cross-sectional areas and failed at 68% less load and 28% less strain than basal chordae. Chordae from the posterior leaflet were 35% thinner and failed at 43% less load and 22% less strain than anterior leaflet chordae. Failure strength was lowest for posterior marginal chordae. Chordae most frequently tore just below the leaflet insertion, in what was often their narrowest section. CONCLUSION: Overall, the marginal chordae and posterior leaflet chordae were thinner and required less strain and load to fail than basal chordae and anterior leaflet chordae, respectively. These results support previous reports of decreased extensibility in marginal chordae. The high incidence of ruptures in the posterior marginal chordae of diseased mitral valves may be due to an inherent weakness in these chordae.

Animals↗
PubMed2002

Biaxial strain distributions in explanted porcine bioprosthetic valves.

BACKGROUND AND AIMS OF THE STUDY: Testing whole explanted porcine bioprosthetic valves provides information on changes the valves undergo over time in vivo, and may help elucidate a possible mechanism for bioprosthetic valve failure. The study aim was to measure the static pressure/strain response of whole explanted porcine bioprostheses. METHODS: Three bioprosthetic valves were explanted prophylactically prior to structural failure. Loading curves (pressure versus strain curves) were generated for these valves using a whole-valve optical strain mapping system. Maximum strain, stiffness, and the occurrence of 'negative compliance' (inverse relationship between cusp strain and applied pressure) were obtained from these curves. RESULTS: All three cusps had very low extensibility (3-10% in the radial direction; 2-4% in the circumferential direction). The non-coronary (NC) cusp was less extensible than the right (RC) or left coronary (LC) cusps in two of the valves. In one valve, the smallest strains were in the RC cusp, where large amounts of calcification were noted. Negative strains were present primarily in one valve. CONCLUSION: The extensibilities of the three explanted valves were lower than those seen in fresh valves, due to either glutaraldehyde fixation and/or extension of the fibrosal corrugations. Furthermore, the uniqueness of the mechanical properties of the NC cusp previously seen in fresh porcine valves remained through glutaraldehyde fixation and stenting. It is concluded that cusp anisotropy and heterogeneity, as well as the occurrence of negative strains seen in fresh porcine valves, are preserved during the fabrication of porcine bioprostheses.

Aged↗