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1.
Acta Biomater ; 102: 149-168, 2020 01 15.
Article in English | MEDLINE | ID: mdl-31734412

ABSTRACT

Collagen fiber networks provide the structural strength of tissues, such as tendons, skin and arteries. Quantifying the fiber architecture in response to mechanical loads is essential towards a better understanding of the tissue-level mechanical behaviors, especially in assessing disease-driven functional changes. To enable novel investigations into these load-dependent fiber structures, a polarized spatial frequency domain imaging (pSFDI) device was developed and, for the first time, integrated with a biaxial mechanical testing system. The integrated instrument is capable of a wide-field quantification of the fiber orientation and the degree of optical anisotropy (DOA), representing the local degree of fiber alignment. The opto-mechanical instrument''s performance was assessed through uniaxial loading on tendon tissues with known collagen fiber microstructures. Our results revealed that the bulk fiber orientation angle of the tendon tissue changed minimally with loading (median ± 0.5*IQR of 52.7° ± 3.3° and 51.9° ± 3.3° under 0 and 3% longitudinal strains, respectively), whereas on a micro-scale, the fibers became better aligned with the direction of loading: the DOA (mean ± SD) increased from 0.149 ± 0.032 to 0.198 ± 0.056 under 0 and 3% longitudinal strains, respectively, p < 0.001. The integrated instrument was further applied to study two representative mitral valve anterior leaflet (MVAL) tissues subjected to various biaxial loads. The fiber orientations within these representative MVAL tissue specimens demonstrated noticeable heterogeneity, with the local fiber orientations dependent upon the sample, the spatial and transmural locations, and the applied loading. Our results also showed that fibers were generally better aligned under equibiaxial (DOA = 0.089 ± 0.036) and circumferentially-dominant loading (DOA = 0.086 ± 0.037) than under the radially-dominant loading (DOA = 0.077 ± 0.034), indicating circumferential predisposition. These novel findings exemplify a deeper understanding of the load-dependent collagen fiber microstructures obtained through the use of the integrated opto-mechanical instrument. STATEMENT OF SIGNIFICANCE: In this study, a novel quantitative opto-mechanical system was developed by combining a polarized Spatial Frequency Domain Imaging (pSFDI) device with a biaxial mechanical tester. The integrated system was used to quantify the load-dependent collagen fiber microstructures in representative tendon and mitral valve anterior leaflet (MVAL) tissues. Our results revealed that MVAL's fiber architectures exhibited load-dependent spatial and transmural heterogeneities, suggesting further microstructural complexity than previously reported in heart valve tissues. These novel findings were possible through the system's ability to, for the first time, capture the load-dependent collagen architecture in the mitral valve anterior leaflet tissue over a wide field of view (e.g., 10 × 10 mm for the MVAL tissue specimens). Such capabilities afford unique future opportunities to improve patient outcomes through concurrent mechanical and microstructural assessments of healthy and diseased tissues in conditions such as heart valve regurgitation and calcification.


Subject(s)
Collagen/physiology , Mitral Valve/physiology , Tendons/physiology , Animals , Biomechanical Phenomena , Cattle , Collagen/ultrastructure , Mechanical Tests , Mitral Valve/ultrastructure , Optical Imaging/methods , Swine , Tendons/ultrastructure
2.
Microsc Res Tech ; 82(7): 1136-1144, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30974026

ABSTRACT

OBJECTIVE: We analysed lncRNA expression profiles in atrial samples from patients with rheumatic mitral valve disease (RMVD) to identify the potential differences in atrial fibrillation (AF)-associated lncRNAs between RMVD patients with AF and sinus rhythm (SR). METHODS: Masson's trichrome staining and scanning electron microscopy were performed to evaluate the tissue morphology. Western blotting was performed to detect the expression of fibrosis-related proteins. Difference analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene co-expression networks were also adopted to perform IncRNA expression profile analysis in atrial samples. RESULTS: Masson's trichrome staining indicated higher contents of fat deposition and fibrous tissue in atrial samples from patients with AF than from patients with SR. Western blotting showed that fibrosis-related proteins, including smad2, TGFß1, MMP9, and TIMP1, were upregulated in atrial samples from patients with AF compared to those from patients with SR. lncRNA expression profiles showed different lncRNA expression levels between RMVD patients with AF and SR. Moreover, GO, KEGG and gene co-expression networks showed consistent results and indicated that differentially expressed genes might contribute to the pathogenesis of AF. CONCLUSION: Our results revealed the potential roles of IncRNAs in the development of AF in patients with RMVD, and lncRNAs may be responsible for morphological and physiological differences in atria between RMVD patients with AF and SR.


Subject(s)
Atrial Fibrillation/genetics , Mitral Valve/pathology , RNA, Long Noncoding/genetics , Rheumatic Heart Disease/genetics , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Humans , Microscopy, Electron, Scanning , Mitral Valve/ultrastructure , RNA, Messenger/genetics , Smad2 Protein/genetics , Tissue Inhibitor of Metalloproteinase-1/genetics , Transforming Growth Factor beta1/genetics , Up-Regulation
4.
J Cardiovasc Transl Res ; 10(4): 374-390, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28462436

ABSTRACT

Decellularized scaffolds represent a promising alternative for mitral valve (MV) replacement. This work developed and characterized a protocol for the decellularization of whole MVs. Porcine MVs were decellularized with 0.5% (w/v) SDS and 0.5% (w/v) SD and sterilized with 0.1% (v/v) PAA. Decellularized samples were seeded with human foreskin fibroblasts and human adipose-derived stem cells to investigate cellular repopulation and infiltration, and with human colony-forming endothelial cells to investigate collagen IV formation. Histology revealed an acellular scaffold with a generally conserved histoarchitecture, but collagen IV loss. Following decellularization, no significant changes were observed in the hydroxyproline content, but there was a significant reduction in the glycosaminoglycan content. SEM/TEM analysis confirmed cellular removal and loss of some extracellular matrix components. Collagen and elastin were generally preserved. The endothelial cells produced newly formed collagen IV on the non-cytotoxic scaffold. The protocol produced acellular scaffolds with generally preserved histoarchitecture, biochemistry, and biomechanics.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis , Mitral Valve , Tissue Engineering/methods , Tissue Scaffolds , Animals , Biomechanical Phenomena , Cell Proliferation , Cells, Cultured , Coculture Techniques , Collagen Type IV/metabolism , DNA Replication , Elastin/metabolism , Fibroblasts/metabolism , Glycosaminoglycans/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Hydroxyproline/metabolism , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Mitral Valve/immunology , Mitral Valve/metabolism , Mitral Valve/transplantation , Mitral Valve/ultrastructure , Stem Cells/metabolism , Sus scrofa , Time Factors
5.
Sci Rep ; 7: 39988, 2017 01 04.
Article in English | MEDLINE | ID: mdl-28051180

ABSTRACT

Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 µm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction.


Subject(s)
Bone Marrow Cells/physiology , Mitral Valve/physiology , Myocardial Infarction/therapy , Tissue Engineering/methods , Tissue Scaffolds , Animals , Biocompatible Materials , Bone Marrow Cells/ultrastructure , Cell Differentiation , Cell Proliferation , Cells, Cultured , Disease Models, Animal , Humans , Male , Mice, Inbred C57BL , Mitral Valve/ultrastructure
6.
Cardiovasc Pathol ; 24(6): 359-67, 2015.
Article in English | MEDLINE | ID: mdl-26345253

ABSTRACT

AIMS: Dysregulation of the transforming growth factor beta (TGF-ß) 1 pathway has been associated with either syndromic or isolated mitral valve (MV) prolapse due to myxoid degeneration (floppy MV). The activation of Smad receptor-mediated intracellular TGF-ß pathway and its effect on adherens junction (AJ) molecular pattern of activated valvular interstitial cells (VICs) in MV prolapse are herein investigated. METHODS: Floppy MV leaflets were obtained from 30 patients (24 males, mean age 55.5±12.7 years) who underwent surgical repair, and 10 age- and sex-matched Homograft Tissue Bank samples served as controls. MV leaflet cellular and extracellular matrix composition, including collagen I and III, was evaluated by histology and transmission electron microscopy. Smad2 active phosphorylated form (p-Smad2), α-smooth muscle actin (α-SMA), and junctional proteins (N-cadherin, cadherin-11, ß-catenin, plakoglobin, plakophilin-2) in VICs were assessed by immunohistochemistry and immunofluorescence and confirmed by immunoblotting. Quantitative real-time polymerase chain reaction was carried out for components of TGF-ß pathway cascade and filamin A (FLN-A). RESULTS: Floppy MV leaflets were thicker (P<.001) and had higher α-SMA+ cell density (P=.002) and collagen III expression (P<.001) than controls. Enhanced p-Smad2 nuclear immunoreactivity (P<.001) and TGF-ß1 gene (P=.045), TIMP1 (P=.020), and CTGF (P=.047) expression but no differences in FLN-A and total Smad2 gene expression levels were found between floppy MV and controls. Higher expression of cadherin-11, either exclusively or in colocalization with N-cadherin, and aberrant presence of plakophilin-2 at the AJ were found in floppy MV vs. CONCLUSIONS: TGF-ß1 pathway activation in nonsyndromic MV prolapse induces VICs differentiation into contractile myofibroblasts and is associated with changes in the molecular pattern of the AJ, with increased cadherin-11 and aberrant plakophilin-2 expression. AJ reinforcement might promote latent TGF-ß1 activation leading to extracellular matrix remodeling in floppy MV.


Subject(s)
Adherens Junctions/chemistry , Mitral Valve Prolapse/metabolism , Mitral Valve/chemistry , Myofibroblasts/chemistry , Transforming Growth Factor beta1/analysis , Actins/analysis , Adherens Junctions/ultrastructure , Adult , Aged , Cadherins/analysis , Case-Control Studies , Cell Transdifferentiation , Collagen Type I/analysis , Collagen Type III/analysis , Desmoplakins/analysis , Extracellular Matrix/chemistry , Female , Filamins/genetics , Humans , Male , Middle Aged , Mitral Valve/surgery , Mitral Valve/ultrastructure , Mitral Valve Prolapse/genetics , Mitral Valve Prolapse/pathology , Mitral Valve Prolapse/surgery , Myofibroblasts/ultrastructure , Phenotype , Phosphorylation , Plakophilins/analysis , Signal Transduction , Smad2 Protein/analysis , Transforming Growth Factor beta1/genetics , beta Catenin/analysis , gamma Catenin
7.
Am J Physiol Heart Circ Physiol ; 309(2): H276-84, 2015 Jul 15.
Article in English | MEDLINE | ID: mdl-26001411

ABSTRACT

The extracellular matrix of the atrioventricular (AV) valves' leaflets has a key role in the ability of these valves to properly remodel in response to constantly varying physiological loads. While the loading on mitral and tricuspid valves is significantly different, no information is available on how collagen fibers change their orientation in response to these loads. This study delineates the effect of physiological loading on AV valves' leaflets microstructures using Second Harmonic Generation (SHG) microscopy. Fresh natural porcine tricuspid and mitral valves' leaflets (n = 12/valve type) were cut and prepared for the experiments. Histology and immunohistochemistry were performed to compare the microstructural differences between the valves. The specimens were imaged live during the relaxed, loading, and unloading phases using SHG microscopy. The images were analyzed with Fourier decomposition to mathematically seek changes in collagen fiber orientation. Despite the similarities in both AV valves as seen in the histology and immunohistochemistry data, the microstructural arrangement, especially the collagen fiber distribution and orientation in the stress-free condition, were found to be different. Uniaxial loading was dependent on the arrangement of the fibers in their relaxed mode, which led the fibers to reorient in-line with the load throughout the depth of the mitral leaflet but only to reorient in-line with the load in deeper layers of the tricuspid leaflet. Biaxial loading arranged the fibers in between the two principal axes of the stresses independently from their relaxed states. Unlike previous findings, this study concludes that the AV valves' three-dimensional extracellular fiber arrangement is significantly different in their stress-free and uniaxially loaded states; however, fiber rearrangement in response to the biaxial loading remains similar.


Subject(s)
Extracellular Matrix/metabolism , Fibrillar Collagens/metabolism , Hemodynamics , Mechanotransduction, Cellular , Mitral Valve/metabolism , Tricuspid Valve/metabolism , Animals , Extracellular Matrix/ultrastructure , Fibrillar Collagens/ultrastructure , Fourier Analysis , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Microscopy, Fluorescence, Multiphoton/methods , Mitral Valve/ultrastructure , Models, Animal , Stress, Mechanical , Swine , Time Factors , Tricuspid Valve/ultrastructure
8.
J Long Term Eff Med Implants ; 25(1-2): 41-53, 2015.
Article in English | MEDLINE | ID: mdl-25955006

ABSTRACT

The atrioventricular valve leaflets (mitral and tricuspid) are different from the semilunar valve leaflets (aortic and pulmonary) in layered structure, ultrastructural constitution and organization, and leaflet thickness. These differences warrant a comparative look at the bending properties of the four types of leaflets. We found that the moment-curvature relationships in atrioventricular valves were stiffer than in semilunar valves, and the moment-curvature relationships of the left-side valve leaflets were stiffer than their morphological analog of the right side. These trends were supported by the moment-curvature curves and the flexural rigidity analysis (EI value decreased from mitral, tricuspid, aortic, to pulmonary leaflets). However, after taking away the geometric effect (moment of inertia I), the instantaneous effective bending modulus E showed a reversed trend. The overall trend of flexural rigidity (EI: mitral > tricuspid > aortic > pulmonary) might be correlated with the thickness variations among the four types of leaflets (thickness: mitral > tricuspid > aortic > pulmonary). The overall trend of the instantaneous effective bending modulus (E: mitral < tricuspid < aortic < pulmonary) might be correlated to the layered fibrous ultrastructures of the four types of leaflets, of which the fibers in mitral and tricuspid leaflets were less aligned, and the fibers in aortic and pulmonary leaflets were highly aligned. We also found that, for all types of leaflets, moment-curvature relationships are stiffer in against-curvature (AC) bending than in with-curvature bending (WC), which implies that leaflets tend to flex toward their natural curvature and comply with blood flow. Lastly, we observed that the leaflets were stiffer in circumferential bending compared with radial bending, likely reflecting the physiological motion of the leaflets, i.e., more bending moment and movement were experienced in radial direction than circumferential direction.


Subject(s)
Aortic Valve/physiology , Mitral Valve/physiology , Pulmonary Valve/physiology , Animals , Aortic Valve/ultrastructure , Biomechanical Phenomena , Microscopy, Electron, Scanning , Mitral Valve/ultrastructure , Pulmonary Valve/ultrastructure , Swine
9.
Heart Lung Circ ; 23(1): 96-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23773781

ABSTRACT

We report a case of 67 year-old female with a 48-year survival of a Starr-Edwards valve at mitral position. The patient underwent Starr-Edwards mitral valve replacement at age of 19 years for mitral stenosis secondary to severe rheumatic valve disease. The patient had experienced a progressive decline in her functional status with increasing dyspnoea on exertion over a two-week period to eventual development of severe shortness of breath at rest prior to hospitalisation. Transoesophageal echocardiogram revealed severe para-prosthetic and intravalvular mitral valve regurgitation. The patient underwent explantation of Starr-Edwards valve and replacement with a mechanical prosthesis. Our case details the longest reported survival of a Starr-Edwards prosthetic valve at mitral area.


Subject(s)
Echocardiography, Transesophageal , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Mitral Valve Insufficiency , Mitral Valve , Female , Follow-Up Studies , Humans , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/ultrastructure , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Time Factors
10.
Connect Tissue Res ; 54(6): 394-402, 2013.
Article in English | MEDLINE | ID: mdl-23869611

ABSTRACT

The aim of this study was to assess structural and biochemical differences in the extracellular matrix of the fetal and adult porcine mitral heart valves in relation to their mechanical characteristics. Using tensile tests it was demonstrated that the material properties of porcine mitral heart valves progressively change with age. The collagen content of the adult heart valve, as estimated by hydroxyproline assay, increases three times as compared with fetal heart valves. Transmission electron microscopy demonstrated that the diameter of collagen fibrils increased in adult heart valves compared with fetal heart valves. The level of collagen cross-linking is lower in the fetal heart valve than the adult heart valve. The reported age differences in the material properties of fetal and adult porcine heart valves were associated with increases in collagen content, the diameter of collagen fibrils and the level of collagen cross-linking. These data lay a foundation for systematic elucidation of the structural determinants of material properties of heart valves during embryonic and postnatal valvulogenesis. They are also essential to define the desirable level of tissue maturation in heart valve tissue engineering.


Subject(s)
Aging/physiology , Mitral Valve/anatomy & histology , Mitral Valve/physiology , Animals , Biomechanical Phenomena , Collagen/metabolism , Cross-Linking Reagents/metabolism , Fetus/anatomy & histology , Fetus/physiology , Mitral Valve/embryology , Mitral Valve/ultrastructure , Sus scrofa
11.
Vet J ; 197(2): 502-5, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23465749

ABSTRACT

Canine myxomatous mitral valve disease is associated with changes in the valve extracellular matrix (ECM). The aim of this study was to examine the use of cell macerated scanning electron microscopy (CMSEM) in evaluating ECM changes in a small sample of valves and to quantify these changes using computer-aided image analysis of sample porosity (a measure of structural disorganisation and collagen loss). The distinct layered structure of the de-cellularised matrix could be seen in the normal valve and there were marked changes in layers and ECM organisation as the disease progressed. Clearly visible and quantifiable, statistically significant changes were found in valve porosity across the entire leaflet thickness and particularly in the valve mid and distal zones. All of these changes are presumed to affect the mechanical function of the valve. In conclusion, CMSEM with computed image analysis can be used to visualise and measure tissue structural changes in a quasi-3-dimensional manner in normal and diseased tissues.


Subject(s)
Connective Tissue/physiology , Dog Diseases/pathology , Mitral Valve Insufficiency/veterinary , Mitral Valve/ultrastructure , Animals , Dogs , Microscopy, Electron, Scanning/veterinary , Mitral Valve/physiology , Mitral Valve Insufficiency/pathology , Porosity
12.
Int J Cardiol ; 167(4): 1603-9, 2013 Aug 20.
Article in English | MEDLINE | ID: mdl-22564390

ABSTRACT

BACKGROUND: Degenerative disease of the mitral valve (DDMV) is always accompanied by lengthening and/or rupture of chordae tendineae. However, the mechanisms and the mode of chordal rupture remain controversial, and the pathologic anatomy of the apparently healthy chordae has mostly been overlooked. We analyze the structural aspects of both ruptured and intact chordae tendineae in DDMV. METHODS AND RESULTS: Structural and ultrastructural microscopic analyses indicate that both the extracellular matrix and the interstitial cells are severely affected. Degenerative chordae show alterations in the synthesis and deposition of collagen and elastin, disorganization of collagen bundles and rupture of collagen fibres, accumulation of proteoglycans and of cellular and vesicular remnants, and cell transformation into a myofibroblast phenotype. Structural disruption makes the spongiosa and the dense collagenous core separate and break. Degeneration of the chordae is segmental, affecting both chordae that are clearly abnormal, and chordae that appear healthy on visual inspection. CONCLUSIONS: Changes in both matrix synthesis and degradation disturb the ordered collagen arrangement and modify the structural and physical properties of the chordae. Progressive structural disruption of the diseased chordae is the cause of chordal rupture. Mitral surgery corrects the damage, but the underlying causes of DDMV are not corrected. Thus, progression of the disease and affectation of additional chordae may be at the basis of the late complications and the recurrent mitral regurgitation which occurs several years after surgery. Our results indicate that a more aggressive approach to surgery may be needed.


Subject(s)
Chordae Tendineae/pathology , Chordae Tendineae/ultrastructure , Mitral Valve Insufficiency/diagnosis , Mitral Valve/pathology , Mitral Valve/ultrastructure , Humans
13.
J Thorac Cardiovasc Surg ; 143(4 Suppl): S38-42, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22285328

ABSTRACT

OBJECTIVE: The study of the mitral valve apparatus and its modifications during functional mitral regurgitation (FMR) is better revealed by 3-dimensional (3D) transesophageal echocardiography (TOE). To plan mitral valve repair by annuloplasty and papillary muscle (PPM) relocation, we proposed a valve repair procedure oriented by the new main features obtained by real-time 3D TOE reconstruction of the mitral valve apparatus. METHODS: Since January 2008, 25 patients with severe FMR before mitral valve repair were examined. Mean coaptation depth and mean tenting area were 1.3 ± 0.2 cm and 3.2 ± 0.5 cm(2), respectively. Intraoperative 2D and 3D TOE were performed, followed by a 3D offline reconstruction of the mitral valve apparatus. A schematic mitral valve apparatus model was obtained. A geometric model like a truncated cone was traced in according to the preoperative measurements. The size of the prosthetic ring was selected preoperatively according to the anterior leaflet surface. The expected truncated cone after annuloplasty was retraced. A conventional normal coaptation depth about 0.6 cm was used to detect the new position of the PPM tips. RESULTS: Offline reconstruction of the mitral valve apparatus and respective truncated cone were feasible in all patients. The expected position of the PPM tips desirable to reach a normal tenting area with a coaptation depth 0.6 cm or less was obtained in all patients. After surgery, all parameters were calculated and no statistically significant difference was found compared with the expected data. CONCLUSIONS: PPM relocation plus ring annuloplasty reduce mitral valve tenting and may improve mitral valve repair results for patients with severe FMR. This technique may be easily and precisely guided by preoperative offline 3D echocardiographic mitral valve reconstruction.


Subject(s)
Blood Vessel Prosthesis Implantation , Echocardiography, Three-Dimensional , Echocardiography, Transesophageal , Mitral Valve Annuloplasty , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Mitral Valve/ultrastructure , Papillary Muscles/diagnostic imaging , Papillary Muscles/surgery , Aged , Blood Vessel Prosthesis Implantation/adverse effects , Humans , Image Interpretation, Computer-Assisted , Italy , Middle Aged , Mitral Valve/physiopathology , Mitral Valve Annuloplasty/adverse effects , Mitral Valve Insufficiency/physiopathology , Papillary Muscles/physiopathology , Predictive Value of Tests , Severity of Illness Index , Treatment Outcome
14.
J Heart Valve Dis ; 19(5): 596-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21053738

ABSTRACT

A 27-year-old male with a six-year history of hypereosinophilic syndrome (HES) presented with a native mitral valve thrombus, despite therapeutic oral anticoagulation. The thrombus was removed, the mitral valve replaced, and subsequent oral anticoagulation maintained at a higher level (INR 3.5). The patient developed two recurrences of mitral valve thrombosis requiring urgent reoperations, and died shortly after the second intervention. A scanning electron microscopy analysis of the native mitral valve thrombus removed during the first cardiac surgery revealed tightly packed thin fibrin strands forming fuzzy irregular structures, with areas of an almost solid fibrin clot. The fibrin networks indicated a heightened thrombin generation, and may account for a diminished susceptibility to intrinsic fibrinolysis. In conclusion, the unfavorably altered compact structure of the fibrin-rich thrombus, which formed despite adequate anticoagulation, might in part explain the recurrent valvular thrombosis. It may also represent a novel prothrombotic mechanism that operates in HES.


Subject(s)
Hypereosinophilic Syndrome/complications , Mitral Valve/pathology , Thrombosis/etiology , Thrombosis/pathology , Adult , Anticoagulants/therapeutic use , Fatal Outcome , Humans , Hypereosinophilic Syndrome/physiopathology , Male , Microscopy, Electron, Scanning , Mitral Valve/ultrastructure , Thrombosis/prevention & control
15.
Diagn Pathol ; 5: 40, 2010 Jun 21.
Article in English | MEDLINE | ID: mdl-20565952

ABSTRACT

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare entity which is an amalgam of mesothelial cells, histiocytes, and fibrin, often found occasionally during cardiac valve replacement. We report a case in a 25-year-old Chinese female with serous mitral stenosis and patent foramen ovale. Routine and immunohistochemical stains and ultrastructure examination revealed the vegetation was predominantly composed of histocytes with scattered mesothelial cells. In fact nodular histiocytic/mesothelial hyperplasia (NHMH) is a similar lesion to MICE. MICE and NHMH could be unified, and NHMH may be a better choice.


Subject(s)
Epithelium/pathology , Mitral Valve Stenosis/pathology , Mitral Valve/pathology , Monocytes/pathology , Adult , Biomarkers/analysis , Epithelium/chemistry , Epithelium/ultrastructure , Female , Fibrin/analysis , Foramen Ovale, Patent/complications , Heart Valve Prosthesis Implantation , Humans , Hyperplasia , Immunohistochemistry , Microscopy, Electron , Mitral Valve/chemistry , Mitral Valve/surgery , Mitral Valve/ultrastructure , Mitral Valve Stenosis/complications , Mitral Valve Stenosis/surgery , Monocytes/chemistry , Monocytes/ultrastructure , Terminology as Topic
16.
EuroIntervention ; 6(1): 54-62, 2010 May.
Article in English | MEDLINE | ID: mdl-20542798

ABSTRACT

AIMS: To evaluate the potential for mitral annular (MA) size reduction using a novel device utilising therapeutic ultrasound (TU). METHODS AND RESULTS: The ReCor device (ReCor Medical, Inc., Ronkonkoma, NY, USA, Investigational device, not for use in human application) was studied in a closed chest canine animal model (35 dogs). Under fluoroscopy, a 12 Fr TU balloon catheter was advanced into the left atrium (transseptal approach). The TU balloon was inflated with contrast-saline, positioned at the MA and energy delivered circumferentially, to heat the tissue locally. Five TU applications were delivered (at least 60W for at least 40 sec). Relative to baseline, mitral valve annular diameter reduction (measured by transthoracic echocardiography) was 8.4% immediately post procedure(p<0.001), 8.6% at one week (p<0.001), 8.8% at two weeks (p<0.001), 9.3% at three weeks (p<0.001), 10.8% at four weeks (p<0.001), 8.6% at three months (p<0.001) and 5.7% at six months (p<0.001). Histology showed an increase in elastin associated with tissue thickening at the annular level. Transmission electron microscopy demonstrated a decrease in diameter of individual collagen fibres in treated regions compared to controls. CONCLUSIONS: Therapeutic ultrasound (TU) energy application to the mitral annulus is feasible percutaneously. A reduction in annular dimensions occurs immediately and appears to be durable without peri-annular damage.


Subject(s)
Catheter Ablation/instrumentation , Mitral Valve/surgery , Ultrasonic Therapy/instrumentation , Animals , Dogs , Echocardiography, Doppler , Elastin/metabolism , Equipment Design , Feasibility Studies , Fibrillar Collagens/ultrastructure , Materials Testing , Microscopy, Electron, Transmission , Mitral Valve/diagnostic imaging , Mitral Valve/metabolism , Mitral Valve/ultrastructure , Models, Animal , Radiography, Interventional , Time Factors
17.
Int. j. morphol ; 27(4): 1217-1222, dic. 2009. ilus
Article in English | LILACS | ID: lil-582076

ABSTRACT

Mitral valve cusps consist mainly of connective tissue and myocardium. Connective tissue fibres within the cusps have been demonstrated to exhibit sex variations in organisation. Mitral prolapse, a disease attributed to defects within the cusps occurs more commonly in females. Sex variations in valvular myocardium however remain to be studied. Possible variations in its organisation may enhance understanding of sex differences in prevalence of mitral prolapse. The aim of this study was to determine anatomical variations of mitral valvular myocardium by sex; by mean a comparative cross-sectional study. A total of 48 (27 male and 21 female) adult heart specimens obtained during autopsy at Nairobi City and Chiromo mortuaries after ethical approval were used. Valvular cusps were then harvested. Four ¡ millimetre sections were made at the area of maximum width for both anterior and posterior cusps. These were processed for paraffin-embedding and sectioning and stained with Masson's trichrome and Weigert's resorcin fuchsin with Van Gieson counterstain to demonstrate cardiac muscle, collagen and elastic fibres. Both anterior and posterior cusps demonstrated three histological laminae, that is, atrialis, fibrosa and ventricularis. Only lamina atrialis contained cardiac muscle. This lamina in males was characterised by a transversely oriented subendothelial myocardial strip while that in females contained compact longitudinal elastic fibres but no muscle. The presence of cardiac muscle in the lamina atrialis may be relatively protective against mitral valve prolapse in males compared to females.


Las cúspides de la valva mitral están constituidas principalmente por tejido conectivo y miocardio. Se ha demostrado que las fibras del tejido conectivo de las cúspides presentan diferencias en la organización según sexo. El prolapso mitral, una enfermedad atribuida a defectos en las cúspides es más frecuente en las mujeres. Las variaciones de sexo en el miocardio valvular sin embargo aún no se han estudiado. Las posibles variaciones en su organización puede mejorar la comprensión de las diferencias de sexo en la prevalencia de prolapso mitral. El objetivo de este estudio fue determinar las variaciones anatómicas del miocardio valvar mitral por sexo, por medio un estudio comparativo de corte transversal. Un total de 48 los especímenes de corazón adulto (se utilizaron 27 hombres y 21 mujeres), obtenidos durante autopsias en la ciudad de Nairobi y desde el depósito de cadáveres Chiromo, después de la aprobación ética. Las cúspides valvares fueron extraídas. Fueron realizadas secciones de cuatro milímetros en el parte más ancha de las cúspides anteriores y posteriores. Estas fueron procesadas por inclusión en parafina, corte y tinción con tricrómico de Masson y fucsina-resorcina de Weigert con contraste Van de Gieson, para demostrar la presencia de músculo cardíaco, fibras colágenas y elásticas. T.


Subject(s)
Humans , Male , Adult , Female , Middle Aged , Sex Characteristics , Mitral Valve/ultrastructure , Cross-Sectional Studies , Microscopy, Electron , Mitral Valve Prolapse/etiology , Mitral Valve/abnormalities
18.
J Heart Valve Dis ; 18(3): 292-9, 2009 May.
Article in English | MEDLINE | ID: mdl-19557986

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: The chordae tendineae, which form an important component of the mitral valve apparatus, experience continuous cyclic loading and are thus well-adapted for effectively storing and dissipating energy. An understanding of their microstructure would be expected to shed light on the mechanism of their remarkable durability. METHODS: In these studies, porcine mitral valve chordae from freshly slaughtered pigs were used. Histological samples of Picrosirius Red-stained and Movat's pentachrome-stained chordae were examined with optical microscopy and laser scanning confocal microscopy. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to study the ultrastructure at high magnification. RESULTS: Both, optical microscopy and SEM revealed that the waviness of collagen fibers was uniform across the thickness of the chordae, with no straight fibers in the core. Wavy fibers and fiber bundles were found to be in skewed-register, rather than transverse. Collagen fiber bundles were found to undulate in a three-dimensional path, rather than the planar waveform, as reported previously. TEM showed that different types of chordae had different fibril configurations. Marginal chordae had smaller diameters but a higher fibril density than did basal and strut chordae. CONCLUSION: The configuration of collagen fibrils in the mitral valve chordae is more complex than initially thought, and different chordae have morphologies that are likely specific to their mechanical role in the mitral apparatus. These findings provide insight into possible improvements for chordal repair surgery, and form a structural basis for accurate computational modeling.


Subject(s)
Chordae Tendineae/ultrastructure , Mitral Valve/ultrastructure , Animals , Biomechanical Phenomena , Collagen/ultrastructure , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Swine
20.
Circulation ; 119(21): 2837-43, 2009 Jun 02.
Article in English | MEDLINE | ID: mdl-19451349

ABSTRACT

BACKGROUND: Management of severe ischemic mitral regurgitation remains difficult with disappointing early and intermediate-term surgical results of valve repair. METHODS AND RESULTS: Forty-four patients with severe (4+) Carpentier type IIIb ischemic mitral regurgitation underwent mitral valve repair, with or without surgical revascularization, by posterior leaflet extension with a patch of bovine pericardium and a remodeling annuloplasty. Serial echocardiography was performed preoperatively, intraoperatively, and postoperatively to assess mitral valve competence. The postoperative functional status of patients was assessed. The average Parsonnet score was 38+/-13. Thirty-day mortality was 11%, and late mortality was 14%. Mean follow-up was 38 months. The actuarial freedom from moderate or severe recurrent mitral regurgitation was 90% at 2 years, whereas 90% of patients were in New York Heart Association class I at 2 years. CONCLUSIONS: Posterior leaflet extension with annuloplasty of the mitral valve for severe type IIIb ischemic regurgitation is a safe, effective method that provides good early and intermediate-term competence of the mitral valve and therefore good functional status.


Subject(s)
Mitral Valve Insufficiency/surgery , Mitral Valve/surgery , Myocardial Infarction/complications , Aged , Aged, 80 and over , Aortic Valve/surgery , Bioprosthesis , Echocardiography, Doppler, Color , Female , Follow-Up Studies , Humans , Internal Mammary-Coronary Artery Anastomosis , Male , Middle Aged , Mitral Valve/ultrastructure , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/etiology , Myocardial Infarction/surgery , Postoperative Complications/mortality , Prostheses and Implants , Retrospective Studies , Suture Techniques , Treatment Outcome , Tricuspid Valve/surgery , Ventricular Function, Left
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