Karyn S. Kunzelman

Bio: Karyn S. Kunzelman is an academic researcher from University of Maine. The author has contributed to research in topics: Mitral valve & Aortic valve. The author has an hindex of 35, co-authored 61 publications receiving 3686 citations. Previous affiliations of Karyn S. Kunzelman include University of Wisconsin-Madison & Central Maine Medical Center.

Stress variations in the human aortic root and valve: the role of anatomic asymmetry.

Abstract: The asymmetry of the aortic valve and aortic root may influence their biomechanics, yet was not considered in previous valve models. This study developed an anatomically representative model to evaluate the regional stresses of the valve within the root environment. A finite-element model was created from magnetic-resonance images of nine human valve-root specimens, carefully preserving their asymmetry. Regional thicknesses and anisotropic material properties were assigned to higher-order elastic shell elements representing the valve and root. After diastolic pressurization, peak principal stresses were evaluated for the right, left, and noncoronary leaflets and root walls. Valve stresses were highest in the noncoronary leaflet (538 kPa vs right 473 kPa vs left 410 kPa); peak stresses were located at the free margin and belly near the coaptation surfaces (averages 537 and 482 kPa for all leaflets, respectively). Right and noncoronary sinus stresses were 21% and 10% greater than the left sinus. In all sinuses, stresses near the annulus were higher than near the sinotubular junction. Stresses vary across the valve and root, likely due to their inherent morphologic asymmetry and stress sharing. These factors may influence bioprosthetic valve durability and the incidence of isolated sinus dilatation.

Finite element analysis of the mitral valve.

Abstract: A finite element model was developed to examine deformation and stress patterns in the mitral valve under systolic loading conditions. This is the first three-dimensional finite element model of the mitral valve, incorporating all essential anatomic components, regional tissue thickness, collagen fiber orientation and related anisotropic material properties. A non-linear, transient, dynamic analysis was performed which included time-dependent loading, leaflet and chordal mass inertial effects and chordal element bi-linearity. The model was first analyzed without either annular or papillary muscle contraction and then with either or both. The hypothesis was that the combination of annular and papillary muscle contraction would have a beneficial effect on valve function. In all models, the computed anterior leaflet principal stresses were tensile and of greater magnitude than those in the posterior leaflet. The principal stress directions were observed to correlate well with collagen fiber orientation. Earlier leaflet coaptation was demonstrated with annular contraction, promoting valve closure, while papillary muscle contraction increased the stress on the chordae tendineae and both leaflets, tending to pull the latter apart. The combination of the two combined these effects, and showed the most even stress distribution. The effects of annular and papillary muscle contraction on valve function were shown to be beneficial by this model, and they can be further elucidated by varying the extent and timing of the individual contractions. This model can be used to examine the effects of pathologic changes, surgical manipulations and proposed material replacements. It can thus aid both the surgeon and the biomedical engineer in improving the materials and techniques available for the repair and/or replacement of mitral valve system components.

Fluid–structure interaction models of the mitral valve: function in normal and pathological states

Abstract: Successful mitral valve repair is dependent upon a full understanding of normal and abnormal mitral valve anatomy and function. Computational analysis is one such method that can be applied to simulate mitral valve function in order to analyse the roles of individual components and evaluate proposed surgical repair. We developed the first three-dimensional finite element computer model of the mitral valve including leaflets and chordae tendineae; however, one critical aspect that has been missing until the last few years was the evaluation of fluid flow, as coupled to the function of the mitral valve structure. We present here our latest results for normal function and specific pathological changes using a fluid-structure interaction model. Normal valve function was first assessed, followed by pathological material changes in collagen fibre volume fraction, fibre stiffness, fibre splay and isotropic stiffness. Leaflet and chordal stress and strain and papillary muscle force were determined. In addition, transmitral flow, time to leaflet closure and heart valve sound were assessed. Model predictions in the normal state agreed well with a wide range of available in vivo and in vitro data. Further, pathological material changes that preserved the anisotropy of the valve leaflets were found to preserve valve function. By contrast, material changes that altered the anisotropy of the valve were found to profoundly alter valve function. The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent significant advances in computational studies of the mitral valve, which allow further insight to be gained. This work is another building block in the foundation of a computational framework to aid in the refinement and development of a truly non-invasive diagnostic evaluation of the mitral valve. Ultimately, it represents the basis for simulation of surgical repair of pathological valves in a clinical and educational setting.

KDIGO clinical practice guidelines for acute kidney injury.

Abstract: tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

Abstract: Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.