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Biomedical subjects

I Vesely

Publications and source records attributed to I Vesely.

At least 19 recordsLinked to original sources
PubMed2001

The effect of elastin damage on the mechanics of the aortic valve.

Porcine bioprosthetic heart valves degenerate and fail mechanically through a mechanism that is currently not well understood. It has been suggested that damage to the elastin component of prosthetic valve cusps could be responsible for changes in the mechanical function of the valve that would predispose it to increased damage and ultimate failure. To determine whether damage to elastin can produce the structural and mechanical changes that could initiate the process of bioprosthetic valve degeneration, we developed an elastase treatment protocol that fragments elastin and negates its mechanical contribution to the valve tissue. Valve cusps were mechanically tested before and after digestion to measure the mechanical changes resulting from elastin damage. Elastin damage produced a decrease in radial and circumferential extensibility (from 43 to 18% strain radially and 12 to 7% strain circumferentially), with a slight increase in stiffness (1.3-2.6kN/m for radial and 10.6-11.9kN/m for circumferential directions). Digestions with trypsin, which does not cleave elastin, confirmed that the changes in mechanics of the circumferential samples were likely due to the nonspecific removal of proteoglycans by elastase, while the changes in the radial samples were indeed due to elastin damage. Removing the mechanical contribution of elastin alters the mechanical behavior of the aortic valve cusp, primarily in the radial direction. This finding implies that damage to elastin will distend the cusps, reduce their extensibility, and increase their stiffness. Damage to elastin may therefore contribute to the degeneration and failure of prosthetic valves.

Animals↗
PubMed2001

Case report: outer sheath rupture may precede complete chordal rupture in fibrotic mitral valve disease.

Rupture mechanics of mitral valve chordae have been difficult to elucidate because most surgical repairs and pathological examinations are performed after the rupture. In an excised anterior leaflet from a fibrotic mitral valve, chordae were observed in an initial phase of rupture. Microscopic sections showed that thinned, nearly ruptured chordal segments were actually chordal cores, containing highly aligned collagen fibers. The outer sheath of elastic fibers, disorganized circumferentially oriented collagen fibers, and endothelial cells that normally surrounds the collagen core apparently had retracted to the extreme ends of the thinned segment, resulting in a bulbous shape, as noted in the chordal rupture literature. In conclusion, these new observations lead us to propose that the rupture of mitral valve chordae is not spontaneous, but may occur over time. The failure of the outer sheath may represent the first phase in a slow, two-part process leading to eventual chordal rupture.

Chordae Tendineae↗
PubMed2000

Role of preconditioning and recovery time in repeated testing of aortic valve tissues: validation through quasilinear viscoelastic theory.

We investigated how preconditioning history and specimen recovery time affect the accuracy of measurements of mechanical properties obtained from sequential, repeated materials testing of porcine aortic valve (PAV) cusps. Strain history protocols were modeled by quasilinear viscoelastic theory and the results compared with the experimental data. Assuming that the model was predictive, the accuracy of predicting experimental data was related to the suitability of the materials testing protocol. We found that the preconditioned state of the PAV material was not unique but was a function of the deformation history that had occurred before the preconditioning cycles. Preconditioning without an adequate rest period between tests increased predictive errors, whereas allowing the material to rest without preconditioning reduced errors. Modeling more of the strain history reduced errors for specimens briefly rested between tests but had no impact on specimens with long rest periods. The smallest predictive errors were obtained for a loading protocol with a 24 h specimen recovery period followed by material preconditioning. We recommend the use of this protocol for estimating material properties of PAV tissues.

Animals↗
PubMed2000

Aortic root dilation prior to valve opening explained by passive hemodynamics.

BACKGROUND AND AIM OF STUDY: During the June 1999 World Symposium on Heart Valve Disease, the mechanism by which the aortic valve opens was discussed. It was suggested, indirectly, that the recently discovered contractile elements within the aortic valve may be responsible. We propose that aortic root dilation does not require any active mechanism within the leaflets or aortic wall, and provide an explanation based entirely on the passive hemodynamics of the aortic valve and root. METHODS AND RESULTS: Previous studies using cine fluoroscopy and sonomicrometry have reported a 5-7% expansion of the aortic root during ventricular contraction, prior to aortic valve opening. Simplified force calculations indicate that the mechanical interactions between the aortic valve and root produce an inward pull on the commissures, constraining the aorta from fully dilating. During systole, as the pressure in the ventricle increases and the aortic valve becomes unloaded, the inward pull on the commissures is reduced and the aorta is able to dilate fully. Aortic dilation therefore occurs before the aortic valve opens. CONCLUSION: We conclude that this mechanism of aortic root dilation prior to valve opening is purely passive, and does not require any active process by the aortic valve or the aortic root.

Aortic Valve↗
PubMed2000

Mechanics of cryopreserved aortic and pulmonary homografts.

BACKGROUND AND AIM OF THE STUDY: The surgical placement of pulmonary valve grafts into the aortic position (the Ross procedure) has been performed for three decades. Cryopreserved pulmonary valves have had mixed clinical results, however. The objectives of this study were to compare the mechanics of cryopreserved human aortic and pulmonary valve cusps and roots to determine if the pulmonary root can withstand the greater pressures of the aortic position. METHODS: Six aortic and six pulmonary valve roots were obtained from the Oxford Valve Bank. They were harvested during cardiac transplantation from hearts explanted for dilated cardiomyopathy (mean patient age 68 years). The whole roots were initially stored frozen at -186 degrees C, then shipped packed on dry ice. After complete thawing, the roots were pressurized whole; test strips were then cut from the valve cusps, roots and sinuses and tested for stress/strain, stress relaxation, and ultimate failure strength. RESULTS: The pulmonary roots were more distensible (30% versus 20% strain to lock-up) and less compliant when loaded to aortic pressures. The pulmonary valve cusp and root tissue also showed greater extensibility and greater stiffness (lower compliance) when subjected to the same loads. CONCLUSION: We conclude that mechanical differences between aortic and pulmonary valve tissues are minimal. The pulmonary root should withstand the forces imposed on it when placed in the aortic position. However, if implanted whole, the pulmonary root will distend about 30% more than the aortic root when subjected to aortic pressures. These geometric changes may affect valve function in the long term and should be appreciated when implanting a pulmonary valve graft.

Aged↗
PubMed2000

Biaxial strain properties of elastase-digested porcine aortic valves.

BACKGROUND AND AIMS OF THE STUDY: Previous studies have suggested that elastin in porcine aortic valve cusps is responsible for restoring collagen fibers to their original configuration between loading-unloading cycles. METHODS: Biaxial loading tests were performed on intact aortic valves before and after elastase treatment to further investigate the role of elastin. RESULTS: Degradation of elastin caused an increase in the radial dimensions of the cusps (mean increase in gauge length, 29%), which corresponded to a significant decrease in radial extensibility (mean decrease, 61%) and a threefold increase in radial stiffness. Changes in circumferential extensibility and stiffness were smaller and, for most cusps, were not statistically significant. Control experiments, in which the valves were treated with buffer only, resulted in the opposite changes in radial dimensions and extensibility (7% decrease in gauge length and doubling of extensibility). CONCLUSION: Changes in the mechanical properties of the aortic valve cusps following incubation in elastase were due to elastin damage, and not incidental to soaking in buffer. As many explanted bioprosthetic valves have mechanical characteristics similar to those of the elastase-treated valves, elastin damage may be a factor in the progressive degeneration and ultimate failure of bioprosthetic heart valves.

Animals↗
PubMed1999

Mineralization of glutaraldehyde-fixed porcine aortic valve cusps in the subcutaneous rat model: analysis of variations in implant site and cuspal quadrants.

When evaluating the efficacy of new antimineralization treatments for bioprosthetic heart valves, subcutaneous implantation in a rat model often is used as an initial test. Although this model is widely used, there still are many aspects of its implementation that have not been investigated. To further investigate several parameters that may affect mineralization in the subcutaneous rat model, portions of glutaraldehyde-treated porcine aortic valve cusps were implanted both ventrally and dorsally into 21-day-old male Sprague-Dawley rats. Cusp quadrants were explanted at 1,2, and 3 weeks postimplantation and the calcium levels determined by atomic absorption spectroscopy. The objective of this study was to determine whether or not different implant locations and/or regions of the cusps affect the degree to which tissue mineralizes in the subcutaneous rat model. A total of 270 tissue specimens were examined. While the specific portion of the cusp implanted did not significantly affect the degree of mineralization, dorsal implantation resulted in significantly more mineralization than abdominal implantation (p = 0.007). As expected, longer implantation time was associated with greater calcification (p = 0.0001). The results of this study indicate that inconsistent placement of tissues in the rat subcutaneous implant model can result in significant differences in the degree of mineralization.

Animals↗
PubMed1999

Quasi-Linear Viscoelastic theory applied to internal shearing of porcine aortic valve leaflets.

The elements of Quasi-Linear Viscoelastic (QLV) theory have been applied to model the internal shear mechanics of fresh and glutaraldehyde-fixed porcine aortic valve leaflets. A novel function estimation method was used to extract the material functions from experimental shear data obtained at one strain rate, and the model was used to predict the material response at different strain rates. In general, experiments and predictions were in good agreement, the larger discrepancies being in the prediction of peak stresses and hysteresis in cyclic shear. In shear, fixed tissues are stiffer (mean initial shear modulus, 13 kPa versus 427 Pa), take longer to relax to steady state (mean tau 2 4,736 s versus 1,764 s) with a slower initial relaxation rate (mean magnitude of G(0), 1 s-1 versus 5 s-1), and relax to a lesser extent than fresh tissues (mean percentage stress remaining after relaxation, 60 versus 45 percent). All differences were significant at p = 0.04 or less, except for the initial relaxation slope. We conclude that shear experiments can complement traditional tensile and biaxial experiments toward providing a complete mechanical description of soft biomaterials, particularly when evaluating alternative chemical fixation techniques.

Animals↗
PubMed1998

Assessment of glutaraldehyde crosslinking efficiency with an amine-specific fluorescent probe.

BACKGROUND: Crosslinking of heart valves with glutaraldehyde involves the binding of amine groups. We have developed a technique that provides an inverse measure of the degree of tissue fixation by quantifying the amount of unbound amines. METHODS: Whole aortic valves were exposed to 0.5% glutaraldehyde solution for 0, 1, 15, and 60 minutes, 6 hours, and 1 and 7 days. Frozen sections were exposed to carboxyfluorescein succinimidyl ester, a fluorescent amine-reactive probe. Images were acquired from each section and processed to separate pixels representing tissue from those representing background. An average fluorescent intensity for each image was calculated and related to the number of unbound amines by comparing with standards. RESULTS: The amount of uncrosslinked amines was observed to decrease exponentially with fixation time and achieved a plateau at 1 day of fixation. A significant difference in the amount of unbound amines also exists between valve leaflets fixed while connected to the root and those excised from the root before fixation. CONCLUSIONS: This amine measurement technique, being sensitive to spatially varying differences in chemical fixation, should be useful in evaluating the efficacy of new fixation protocols.

Amines↗
PubMed1998

The role of elastin in aortic valve mechanics.

Recent morphologic observations of elastin structures in aortic valves suggest that elastin is mechanically coupled to collagen. Since the mechanical stiffness of elastin is considerably lower than that of collagen, and aortic valves contain relatively little elastin, the mechanical importance of elastin in heart valve function is not clear. We have hypothesized that elastin acts to return the collagen fiber structure back to a resting configuration between loading cycles. The objectives of this research were therefore to elucidate the mechanical relationship between elastin and collagen structures within the aortic valve. To isolate elastin in a morphologically intact state, whole porcine aortic valve leaflets were digested in 0.1 N sodium hydroxide solution (NaOH) at a temperature of 75 degrees C for 45 min. Elastin structures from the fibrosa and ventricularis were tested mechanically, and their loading curves compared to those of the original leaflet layers and to whole cusps. The elastin structures generated very low forces, having an elastic modulus only 0.05% that of the whole tissue. The contribution of elastin to tissue mechanics was significant at low strains and differed between the fibrosa and the ventricularis. Elastin tended to dominate the distensibility curves of the radial ventricularis, but participated very little in the fibrosa. The low but significant tensions produced by the elastin structures of the aortic valve, together with previously observed elastin morphology as well as the measurable preload of elastin, suggest that the purpose of elastin in the aortic valve leaflet is to maintain a specific collagen fiber configuration and return the fibers to this state, once external forces have been released.

Animals↗
PubMed1998

Comparison of the compressive buckling of porcine aortic valve cusps and bovine pericardium.

BACKGROUND AND AIMS OF THE STUDY: Compressive buckling at sites of sharp leaflet flexure has been implicated as a mechanism of failure in porcine xenografts. The potential for such buckling to cause damage in new-generation pericardial valves, however, has not been examined. METHODS: Clinical-grade bovine pericardium fixed in 0.625% glutaraldehyde was cut into 5 mm-wide strips. Fresh porcine aortic valve leaflets were fixed flat in 0.625% glutaraldehyde and 5 mm-wide circumferential strips were cut. These tissues were bent to various curvatures, held bent with sutures, histologically processed, and sectioned and stained with hematoxylin and eosin. Images of the specimens were acquired by computer and the depth of compressive buckling, thickness of the specimen, and local curvature were measured. RESULTS: Porcine tissue showed a progressive increase in depth of buckling as both thickness and curvature increased, while bovine pericardium had minimal buckling at all curvatures. Porcine tissues buckled to a mean (+/- SEM) fractional depth of 0.23+/-0.012 while bovine pericardium buckled to only 0.09+/-0.006. CONCLUSIONS: These data suggest that the internal fibrous structure of bovine pericardium may tolerate high bending curvatures better than porcine aortic valve leaflets when stiffened and cross-linked with glutaraldehyde. This may explain the apparently good durability of current generation pericardial valves.

Animals↗
PubMed1997

Viscoelasticity of dynamically fixed bioprosthetic valves. II. Effect of glutaraldehyde concentration.

OBJECTIVE: We have previously shown the benefits of dynamic fixation over conventional static fixation of bioprosthetic valves. In an attempt to increase the durability of bioprosthetic heart valves, we explored the benefit of low-concentration glutaraldehyde dynamic fixation. METHODS: Pig aortic valves obtained fresh from the abattoir and excised with the entire root were dynamically fixed in glutaraldehyde phosphate buffer solutions varying in concentration from 0.05% to 2.5%. Denaturation temperatures were measured and mechanical testing was performed at low (3 mm/sec) to high physiologic rates (30 mm/sec) at 37 degrees C in isotonic modified Hanks solution. RESULTS: When fixed dynamically in 0.05% glutaraldehyde solution for 24 hours, the tissue reached a degree of cross-linking (denaturation temperature = 82.8 degrees +/- 0.6 degree C) significantly higher than that obtained for 0.05% static fixation (denaturation temperature = 79.3 degrees +/- 0.9 degree C) (p < 0.05) but similar to that for conventional static fixation in 0.5% glutaraldehyde solution (denaturation temperature = 83.5 degrees +/- 0.3 degree C). After fixation in low-concentration glutaraldehyde (0.05%), final relaxation slopes and moduli in the circumferential direction were significantly higher than those for the statically fixed tissue but similar to those for the fresh tissue. However, both dynamic and static fixation had the effect of increasing tissue extensibility to similar extents in both directions, irrespective of glutaraldehyde concentration. CONCLUSIONS: Dynamic glutaraldehyde fixation of a porcine aortic valve at lower concentrations resulted in a better degree of cross-linking and a material with biomechanical properties that more closely mimic those of natural heart valve tissue.

Animals↗
PubMed1997

In vivo and in vitro models of calcification in porcine aortic valve cusps.

Both in vivo and in vitro models have been developed to study the initiation and progression of dystrophic calcification of bioprosthetic heart valves. Circulatory in vivo models have proven to be the most predictive of the success of a new valve designs or anticalcification schemes; however, these experiments are time consuming and expensive. An appealing alternative to circulatory implantation is the sub-cutaneous rat implantation model. This model is inexpensive and calcification occurs rapidly. Recent studies have shown, however, that some anticalcification methods work well in the subcutaneous model but are ineffective in the circulatory model. In vitro models would provide the most convenient method for testing new anticalcification strategies but, to date, no in vitro test system has been developed which produces calcification of rates and with morphology comparable with that in vivo models. We have also studied the effects of collagen damage and cell extraction on the calcification of porcine aortic valve cusps both in vitro and in the subcutaneous rat model, and found significant differences in the patterns of mineralization. The objectives of this paper therefore are to compare and contrast the different experimental protocols and procedures reported in the literature to better define the effects of different model systems on the calcification process.

Animals↗
PubMed1996

Dynamic glutaraldehyde fixation of a porcine aortic valve xenograft. I. Effect of fixation conditions on the final tissue viscoelastic properties.

Sixty porcine aortic valves were fixed under dynamic conditions at specific durations, pressures and vibration rates in a 0.5% glutaraldehyde phosphate buffer (pH 7.4, 0.2 M). Tensile relaxation tests were performed at low through high extension rates (0.3, 3 and 30 mm s-1) and tissue denaturation temperatures were determined by the hydrothermal isometric tension method. Conventional statically fixed valves and fresh valves were used as controls. No differences between dynamic and static treatment were observed at pulsation rates above those expected in the physiological range (i.e. above 1.2 Hz) or at higher pressures such as 30 mmHg. However, differences in both stress relaxation rates and denaturation temperatures were delineated in milder fixation conditions, i.e. at low pressures (< 4 mmHg) and low vibration rates similar to that of the normal heart beat (approximately 1.2 Hz). In these conditions the relaxation rate of the dynamically fixed tissue (-7.4 +/- 0.7% of stress remaining per log(s)) was similar to that of the fresh tissue (-6.7 +/- 1.2% log(s-1)) and significantly higher than the statically treated tissue (-3.9 +/- 1.7% log(s-1)). The rates of stress relaxation appeared to be strain rate dependent in both radial and circumferential directions when the tissues were strained at physiological rates during testing (> approximately 15000% min-1). Dynamically treated valves showed higher denaturation temperatures (mean +/- SD) (89.4 +/- 0.5 degree C) compared with the statically fixed (82.7 +/- 1.4 degrees C) or untreated (fresh) valves (65.5 +/- 0.8 degree C). The results suggest a higher degree of internal cross-linking owing possibly to enhanced penetration of the glutaraldehyde reagent and a greater accessability of reactive cross-linking sites on the collagen molecules. Better stress relaxation rates are likely associated with an increase in potential shearing between adjacent collagen fibres thus preserving the natural stress-reducing mechanism of the fresh, untreated valves. The dynamically treated valves therefore possess characteristics that may enable them to better resist long-term mechanical fatigue and in vivo degradation.

Animals↗
PubMed1996

Morphology of porcine aortic valve cusp elastin.

BACKGROUND AND AIM OF STUDY: While the structure and function of heart valve cusp collagen have been relatively well defined, the role and morphology of elastin remains poorly understood, despite the fact that it comprises up to 13% of the cusp dry weight. MATERIAL AND METHODS: The elastin structure of 24 hot-alkali-digested porcine aortic valve cusps was investigated with scanning electron microscopy. Elastin structures were categorized according to their morphology and a model of the distribution of these structures within the cusp was developed. RESULTS: The two main types of elastin observed, amorphous and fibrillar, were further categorized based on their morphology. Amorphous structures included continuous sheet, sheet with integrated fibers on the surface and sheet with fenestrations. Fibrillar structures identified were loose fibers, loose mesh/woven fibers and compact mesh. By imaging samples of digested fibrosa and ventricularis that had been microdissected apart, we were able to produce maps of the elastin structure in the two layers. The ventricularis contains a large continuous sheet of amorphous or compact mesh elastin that covers the entire layer. Elastin in the fibrosa is much more complex, consisting of large tubes that emerge from the aortic attachment and extend circumferentially across the cusp. The tubes, constructed of amorphous fenestrated sheet and loose mesh elastin, likely surround the large circumferential collagen bundles observed in the fibrosa. CONCLUSIONS: The elastin structures that we have identified help explain the measured mechanics of this tissue and suggest that collagen and elastin are highly integrated. As a result, we believe that elastin plays an important functional role in the cusp and that a full explanation of heart valve cusp mechanics must incorporate the contributions of both collagen and elastin.

Animals↗
PubMed1995

The hybrid xenograft/autograft bioprosthetic heart valve: in vivo evaluation of tissue extraction.

The major functional problem with bioprostheses is poor long-term durability. Bioprosthetic valves fail because of calcification and mechanical fatigue, both of which result from the glutaraldehyde fixation process. In an effort to develop a biologically active, non-cross-linked bioprosthetic valve, we devised a cellular extraction process. We tested the mechanical integrity of the processed valves and cultured both human and porcine cells on this material. To test the potential for calcification, we implanted strips of fresh, extracted, and glutaraldehyde-treated porcine heart valve tissue subcutaneously into 3-week-old Sprague Dawley rats for 21 days. We used atomic absorption spectroscopy to measure the extent of calcium accumulation and histopathologic assessment to evaluate the antigenic response. We found that the cell extraction process significantly reduced the propensity of the material to calcify in vivo (mean +/- standard deviation, 4.12 +/- 1.02 mg/g calcium extracted versus 10.75 +/- 3.9 mg/g calcium fresh versus 79.6 +/- 18.3 mg/g calcium glutaraldehyde fixed) but increased the antigenicity, as evidenced by increased cellular activity and resorption. Although they may reduce calcification, conventional detergent-based cell extraction techniques do not completely remove porcine aortic valve antigens and may in fact increase the antigenicity of the valve cusp material.

Animals↗