Functional mitral regurgitation (FMR) is a significant complication of left ventricular dysfunction and strongly associated with a poor prognosis. In this study, we developed a patient-specific finite element (FE) model of the mitral apparatus in a FMR patient which included: both leaflets with thickness, annulus, chordae tendineae, and chordae insertions on the leaflets and origins on the papillary muscles. The FE model incorporated human age- and gender-matched anisotropic hyperelastic material properties, and MV closure at systole was simulated. The model was validated by comparing the FE results from valve closure simulation with the in vivo geometry of the MV at systole. It was found that the FE model could not replicate the in vivo MV geometry without the application of tethering pre-tension force in the chordae at diastole. Upon applying the pre-tension force and performing model optimization by adjusting the chordal length, position, and leaflet length, a good agreement between the FE model and the in vivo model was established. Not only were the chordal forces high at both diastole and systole, but the tethering force on the anterior papillary muscle was higher than that of the posterior papillary muscle, which resulted in an asymmetrical gap with a larger orifice area at the anterolateral commissure resulting in MR. The analyses further show that high peak stress and strain were found at the chordal insertions where large chordal tethering forces were found. This study shows that the pre-tension tethering force plays an important role in accurately simulating the MV dynamics in this FMR patient, particularly in quantifying the degree of leaflet coaptation and stress distribution. Due to the complexity of the disease, the patient-specific computational modeling procedure of FMR patients presented should be further evaluated using a large patient cohort. However, this study provides useful insights into the MV biomechanics of a FMR patient, and could serve as a tool to assist in pre-operative planning for MV repair or replacement surgical or interventional procedures.
While the role of platelets in hemostasis is well characterized from a biological perspective, the biophysical interactions between platelets and their mechanical microenvironment are relatively unstudied. The field of cellular mechanics has developed a number of approaches to study the effects of extracellular matrix (ECM)-derived mechanical forces on various cells, and has elucidated that integrin-cytoskeleton-mediated force transduction governs many cellular processes. As platelets adhere and spread via molecular machinery that is similar to that which enables other cells to mechanosense and mechanotransduce forces from their biophysical microenvironment, platelets too are likely governed by the same overarching mechanisms. Indeed, recent platelet mechanobiology studies have revealed that key aspects of platelet physiology and activation are regulated by the mechanical and spatial properties of the ECM microenvironment. At the same time, there are also key differences that make platelets unique in the world of cells - their size, origin as megakaryocyte fragments, and unique αIIbβ3 integrin - render their mechanosensing activities particularly interesting. The structurally "simple," anucleate nature of platelets coupled with their high actin concentration (20% of total protein) and integrin density [1] seem to make them ideal for mechanical force generation and transmission. Further studies will enhance our understanding of the role of platelet mechanobiology in hemostasis and thrombosis, potentially leading to new categories of diagnostics that investigate the mechanical properties of clots to determine bleeding risk, as well as therapies that target the mechanotransduction signaling pathway to alter the stability of clots.
by
Andrew W. Siefert;
Jean Pierre Rabbah;
Kevin J. Koomalsingh;
Steven A. Touchton;
Neelakantan Saikrishnan;
Jeremy R. McGarvey;
Robert C. Gorman;
Joseph H. Gorman, lll;
Ajit Yoganathan
Background: This study was undertaken to evaluate an in vitro mitral valve (MV) simulator's ability to mimic the systolic leaflet coaptation, regurgitation, and leaflet mechanics of a healthy ovine model and an ovine model with chronic ischemic mitral regurgitation (IMR).
Methods: Mitral valve size and geometry of both healthy ovine animals and those with chronic IMR were used to recreate systolic MV function in vitro. A2-P2 coaptation length, coaptation depth, tenting area, anterior leaflet strain, and MR were compared between the animal groups and valves simulated in the bench-top model.
Results: For the control conditions, no differences were observed between the healthy animals and simulator in coaptation length (p = 0.681), coaptation depth (p = 0.559), tenting area (p = 0.199), and anterior leaflet strain in the radial (p = 0.230) and circumferential (p = 0.364) directions. For the chronic IMR conditions, no differences were observed between the models in coaptation length (p = 0.596), coaptation depth (p = 0.621), tenting area (p = 0.879), and anterior leaflet strain in the radial (p = 0.151) and circumferential (p = 0.586) directions. MR was similar between IMR models, with an asymmetrical jet originating from the tethered A3-P3 leaflets.
Conclusions: This study is the first to demonstrate the effectiveness of an in vitro simulator to emulate the systolic valvular function and mechanics of a healthy ovine model and one with chronic IMR. The in vitro IMR model provides the capability to recreate intermediary and exacerbated levels of annular and subvalvular distortion for which IMR repairs can be simulated. This system provides a realistic and controllable test platform for the development and evaluation of current and future IMR repairs.