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Biomedical subjects

D Boughner

Publications and source records attributed to D Boughner.

15 recordsLinked to original sources

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↗

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↗

Porcine pulmonary and aortic valves: a comparison of their tensile viscoelastic properties at physiological strain rates.

Pulmonary valve autografts and allografts have been recently reported as being clinically effective for the replacement of the diseased aortic valve. While the biomechanics of the aortic valve have been widely studied, there is little information available about the mechanical properties of the pulmonary valve. We felt that it was necessary to investigate the mechanical properties of the pulmonary valve to determine if it is mechanically suitable as a long term replacement for the aortic valve. We employed physiological strain rate tensile testing to investigate the stress-strain and stress relaxation behaviour of 44 aortic and 40 pulmonary valve cusp strips cut in the radial and circumferential directions, in fresh and glutaraldehyde fixed states. Stress-strain and stress relaxation tests were performed on each test strip at extension rates of 40 mm/s, 4 mm/s and 0.4 mm/s. In all but one mechanical parameter, we found no difference between aortic and pulmonary valve tissues. The extensibilities and relaxation rates were similar, but the aortic valve tissue had a greater average modulus (p = 0.0005) than the pulmonary valve tissue (i.e. 7.41 MPa vs. 5.86 MPa respectively). Since bioprostheses are often constructed from materials with mechanical properties very different from those of the aortic valve, like pericardium, the slight difference between aortic and pulmonary valves is unlikely to affect the operation of the pulmonary valve in the aortic position. The pulmonary valve could therefore be considered mechanically acceptable as a replacement for the aortic valve.

Animals↗

The distribution and morphology of aortic valve cusp lipids.

During dissections of porcine aortic valves, we noted clusters of spherical droplets, roughly 50 micrometers in size, within the central spongiosa of the valve cusps. Oil red-O staining of fresh tissues confirmed that the clusters were lipids, and thin layer chromatography showed that they consisted mainly of free cholesterol and triglycerides, with some cholesterol ester. The distribution of these clusters in 60 cusps from 20 porcine aortic valves was mapped using computerized morphometry. The ventricularis was peeled back to expose the spongiosa, and the spatial distribution of the lipid droplets was analyzed using a stereological point counting method. Computer averaging of lipid density images was done to obtain a mean distribution map of lipid occurrence. This distribution map suggests that porcine aortic valve lipids are found predominantly at the base of the valve cusps, and are conspicuously absent from the coaptation regions and the free edge. Moreover, 19/20 valves had lipids in the left coronary cusp and all 20 valves had lipids in at least two of the three cusps. Endogenous lipids are therefore ubiquitous in porcine aortic valves and may play a role in the calcification of xenograft bioprostheses.

Animals↗

Malposition of transvenous pacing lead in the left ventricle.

Malposition of pacemaker leads has been described in several locations but rarely in the left ventricle. The incidence and clinical course of this pacemaker complication are unknown. We describe clinical, electrocardiographic, chest X ray, and echocardiographic findings in four patients in whom the transvenous pacing lead was inadvertently placed through the interatrial septum and mitral valve into the left ventricle. In these patients, lead misplacement was not recognized at the time of implantation and lead malposition was diagnosed a mean of 2 years later. All four patients had right bundle branch block configuration paced complexes. In retrospect, chest X rays suggested atypical lead position in all, but the initial posterior-anterior and lateral chest X rays were misinterpreted and contributed to the delay in diagnosis. When lead misplacement in the left ventricle was considered it was confirmed by two-dimensional echocardiography. One patient subsequently presented with a stroke and the remainder were diagnosed when they presented with other unrelated problems. Pacing thresholds were normal at the time of implantation and behaved normally during follow-up. The patient presenting with stroke was anticoagulated and the other three have been managed expectantly without anticoagulation. Diagnosis of left ventricular lead malposition is not difficult but requires a high index of suspicion. A 12-lead ECG and posterior-anterior and lateral chest X rays after implantation can be diagnostic. Patients with pacing lead in the left ventricle may remain asymptomatic with normal lead function during long-term follow-up. Anticoagulation should be considered when this problem comes to attention for the first time during follow-up.

Aged↗

Left atrial bacterial mural endocarditis.

An unusual case of Staphylococcus aureus endocarditis confined to the mural left atrium is presented. Echocardiographic studies revealed a 1.5 x 2.0-cm vegetation mimicking a myxoma situated in the path of a mitral regurgitant jet on a color Doppler test. Emboli to upper and lower extremities and brain complicated the patient's preoperative course. Surgical excision and pathologic examination confirmed this rare occurrence.

Diagnosis, Differential↗

Effects of dynamic fixation on shear behaviour of porcine xenograft valves.

To evaluate an alternative valve fixation technique, we measured the ability of glutaraldehyde-fixed valve tissue to undergo internal shearing during bending. Porcine aortic valves were fixed statically using conventional means, and dynamically while opening and closing repeatedly in a pulse tank. Using a polarized light microscopy technique developed previously, we measured shear deformation angles in thin sections of bent leaflet tissue and calculated shear strains. Statically-fixed leaflet tissue sheared only 1.2% +/- 2.29% (Mean +/- SD) when bent to curvatures of 2.0 mm-1, while dynamically-fixed tissue sheared 5.1% +/- 2.63% (significant at P less than 0.05). It is likely that dynamic fixation increases the ability of prosthetic valve leaflets to shear during bending by reducing the number of interfibre cross-links that would otherwise impede such deformations. Because shear strains reduce internal fibre strains and protect the leaflets against fatigue, prosthetic valves constructed from dynamically fixed tissue should experience lower stresses and hence last longer.

Biomechanical Phenomena↗

Mechanical testing of cryopreserved aortic allografts. Comparison with xenografts and fresh tissue.

Reports indicate that cryopreserved aortic valve allografts have a better long-term survivability than other bioprostheses, such as the porcine xenograft. Unlike xenografts, allograft valves do not require treatment with glutaraldehyde and may therefore retain much of their original mechanical function. The effects of cryopreservation on the mechanical integrity of collagen fibers and mucopolysaccharides, however, are still largely unknown. We therefore compared the mechanical behavior of cryopreserved allograft leaflet material to that of fresh tissue and xenografts by measuring their bending stiffness (nine strips of tissue) and their uniaxial tensile stress/strain and stress/relaxation behavior (six strips of each tissue type). The bending tests showed no significant difference between the pliability of cryopreserved allografts and fresh pig aortic valve tissue, but the xenograft material was significantly stiffer than both (p less than 0.001). The mean circumferential tensile elastic moduli of the allografts, fresh tissue, and xenografts at a stress of 300 kPa were 9.1 +/- 5.4 MPa, 13.0 +/- 1.7 MPa, and 12.5 +/- 3.0 MPa, respectively, and were not significantly different from each other. We also found that the transition from a low to a high modulus on the stress/strain curves, a measure of extensibility, occurs at 23%, 22%, and 12% strain for the three materials. There was no significant difference between the allograft and the fresh tissues, but the xenograft material was less extensible than the other two (p less than 0.001). The xenograft tissue also had significantly lower rates of stress relaxation than the other two materials (p less than 0.005). Thus no detectable differences were found between the mechanical behavior of the cryopreserved allograft aortic leaflets and fresh tissue, whereas the xenograft material was less extensible and less capable of relaxing than both the allograft and fresh tissue. The ability of allografts valves to respond to tensile and flexural stresses in a manner similar to that of the natural aortic valve may therefore contribute to their good in vivo survivability.

Aorta↗

Analysis of the bending behaviour of porcine xenograft leaflets and of natural aortic valve material: bending stiffness, neutral axis and shear measurements.

Flexibility of the materials used in the construction of bioprosthetic heart valves is essential for proper valve operation. We therefore examined the bending behaviour of glutaraldehyde treated porcine aortic valve cusps in comparison with fresh aortic valve tissue. We repeatedly bent a total of 35 strips of fresh and treated tissue to curvatures ranging from 0.2 to 2.2 mm-1. We compared the stiffness of the two materials between circumferential and radial bending, natural and reverse curvatures and constant or variable tensile stress (0.8-40 kPa). Our results showed a weak positive relationship between bending stiffness and applied tensile stress and a strong positive dependance of stiffness on tissue thickness (t). For the fresh tissue, the bending stiffness increased in proportion to t1.14 while for the glutaraldehyde treated tissue it increased with t2.18. Fourteen strips of fresh and treated tissue were also histologically processed, sectioned and examined with polarized light microscopy. Collagen fiber wavelengths and shear deformations were measured utilizing the tissue banding patterns produced by polarized light microscopy. The neutral axis of bending was found to lie very close to the outer surface of the tissue, suggesting that aortic leaflets have a very low compressive elastic modulus. The shear strains measured in fresh tissue were 10 +/- 2.7% vs 3 +/- 4.4% for the treated, indicating a stiffening of the tissue following glutaraldehyde fixation. We conclude that both natural and bioprosthetic valve cusps have a complex flexural behaviour that cannot be modeled using simple bending principles, although the bioprosthetic material more closely approximates the simple beam than does the fresh. The non-linear elastic modulus, high compressibility and shearing between fiber layers are likely responsible for the observed behaviour of the fresh tissue, while the cross-linking and dehydrating effects of glutaraldehyde are believed to be responsible for the alteration in bending properties observed in the treated tissue. Our study suggests that bioprosthetic valve material does not adequately mimic the mechanics of the natural valve tissue, and that the current glutaraldehyde fixation process eliminates many of the beneficial, stress-reducing properties of the aortic leaflet.

Animals↗

Tissue buckling as a mechanism of bioprosthetic valve failure.

Current reports indicate that collagen fiber disruption resulting from cyclic leaflet bending is a factor determining long-term durability of bioprosthetic heart valves. Examination of the opening characteristics of porcine xenografts has shown two areas of high bending curvature that correlate well with sites of leaflet tearing. These are at the free edge and near the attachment of the leaflets to the aortic root. To determine the potential effects of sharp bends in leaflet material, we examined 15 strips each of fresh and glutaraldehyde-treated porcine aortic valve tissue. Leaflet strips were bent to curvatures of 0.18 mm-1 to 6.67 mm-1, histologically processed, sectioned, and examined under a light microscope. We observed severe compressive buckling in the samples taken from bioprosthetic valves but little in the fresh-tissue samples. At physiological curvatures (less than 0.28 mm-1), no buckling occurred in the fresh tissue; at high bending curvatures (2.0 mm-1), the depth of buckling observed in the treated tissue was 100% greater than that in the fresh. We believe that porcine xenograft failure is related to compressive buckling of the aldehyde-treated tissue and is mediated by the systematic breaking of collagen fibers at the site of buckling. We suggest that alternative valve designs and preservation techniques be employed to prevent such abnormal leaflet deformations.

Animals↗

Myopathy in primary systemic amyloidosis.

Involvement of the peripheral nervous system by amyloidosis is common. It is less well recognized that amyloid can directly infiltrate and weaken skeletal muscle. We report a case of a 73-year-old woman, known to have cardiac amyloidosis, who developed profound weakness secondary to amyloid myopathy. Review of the 8 other well documented cases in the literature has revealed a rather homogeneous syndrome. Proximal weakness, muscle stiffness, pseudohypertrophy and myalgia constitute the principal features. This syndrome usually develops in cases with well recognized generalized amyloidosis. Amyloid is deposited within the basal lamina of blood vessels and muscle fibers.

Aged↗

Usefulness of noninvasive studies for diagnosis of right ventricular dysplasia.

The value and limitations of echocardiography and cardiac scintigraphy in the diagnosis of right ventricular (RV) dysplasia were assessed. Criteria that defined RV dysfunction were developed first using data from 40 normal subjects. The sensitivity and specificity of these criteria to detect RV dysplasia were then determined in 44 patients suspected of having RV dysplasia. In these patients the presence (14 patients) or absence (30 patients) of RV dysplasia had been established using cardiac catheterization data, which included contrast RV cineangiograms. Mean RV end-diastolic and end-systolic diameters, and RV/left ventricular (LV) ratios of end-diastolic and end-systolic diameters and end-diastolic and end-systolic volumes were greater in patients with RV dysplasia (p less than 0.001). Using cardiac scintigraphy, all patients with RV dysplasia were identified by an RV/LV end-systolic volume greater than 1.8; exercise RV ejection fraction less than 50%; or exercise RV wall motion score more than 1. Using echocardiography, RV contraction abnormalities were seen in 80% of patients with RV dysplasia. The specificities, even in this selected population, were less than 100%. Thus, normal echocardiographic and scintigraphic results can be used instead of RV contrast cineangiography to exclude the diagnosis of RV dysplasia.

Adult↗

Effect of dynamic glutaraldehyde fixation on the viscoelastic properties of bovine pericardial tissue.

We have previously proposed dynamic fixation as an alternative method to fix a porcine aortic heart valve xenograft with better tissue fixation and better preservation of its natural biomechanical properties. Bovine pericardium was fixed under dynamic conditions, low pressures (< 4 mmHg) and low vibration rate (1.2 Hz) in a 0.5% glutaraldehyde phosphate buffer (pH 7.4, 0.2 M). After fixation, tensile testing (i.e. relaxation and stress-strain curves) was performed at low and high extension rates (3 and 30 mm s(-1)) and tissue denaturation temperatures were determined by the hydrothermal isometric tension method. Conventional fresh and statically fixed pericardium were used as controls. In this instance, we found no significant biomechanical differences between the dynamically and statically fixed pericardial tissue (e.g. moduli and stress relaxation). However, differences in tissue extensibility were delineated, since the extensibility of the dynamically fixed tissue was closer to that of the fresh tissue compared to that of the statically fixed tissue. The final relaxation rate of the dynamically fixed tissue (-3.5 +/- 1.0% of stress remaining per log(second)) was similar to that of the statically fixed tissue (-3.2 +/- 0.60% log(s(-1))) and significantly lower than the fresh tissue(-9.5 +/- 1.2% log(s(-1))). The denaturation temperatures of the dynamically fixed pericardial tissue (mean +/- SD) (86.0 +/- 1.2 degrees C) and the statically fixed (85.2 +/- 1.6 degrees C) were similar but significantly higher than that of the untreated (fresh) valves (69.3 +/- 0.4 degrees C). The results suggest a similar degree of internal cross-linking for both statically and dynamically fixed pericardium. Although fundamental structural differences exist between both porcine and bovine xenograft tissue, how these differences contribute to biomechanical differences in the effects of dynamic versus static fixation remain to be explained.

Animals↗

Echocardiographic diagnosis of myocardial abscess complicating myocardial infarction.

The relative incidence of myocardial abscesses occurring in the presence of acute or chronic ischemic heart disease is unknown. Clinical presentation usually involves nonspecific signs of sepsis, and the diagnosis often becomes apparent only when extensive myocardial destruction has occurred. Early diagnosis can greatly reduce morbidity and mortality rates. Echocardiography is a readily accessible and accurate method of diagnosing abscesses both in the presence or absence of endocarditis. We describe the appearance of a myocardial abscess complicating myocardial infarction.

Abscess↗