Morphological Structure And Mechanical Characteristics Analysis And Computational Simulation Research Of Mitral Valve Chordae Tendineae

Heart disease endangers human health.In 2018,the prevalence of cardiovascular disease in China experiences uprising.It is estimated that there are 290 million patients,and cardiovascular diseases account for nearly 20%of the total population,ranking first in the mortality rate of major diseases.It is increasing year by year.The number of patients undergoing heart valve replacement surgery will reach 850,000 in 2050 in the whole world.The mitral valve is a complex organ,and the chordae tendineae is a component of the mitral valve.The function of this structure is to assist the proper coaptation of the mitral valve during the systole.When the valve leaflets are under pressure,the force is evenly distributed and transmitted to the papillary muscles via chordae,chordal failure is the main cause of mitral regurgitation.A study of the chordae can assist in improving understanding of valve disease,and optimizing clinical treatment to cope with the chordal rupture.A better understanding of the chordae is especially beneficial for optimizing mitral valve computational model and chordal tissue engineering.Therefore,study on morphology,biomechanics and histology of chordae is of great significance.In this study,the chordae were traditional grouped according to the leaflet types to study the structure and mechanical properties of each group in the physiological conditions.Then the anterolateral and posteromedial papillary muscles and the corresponding chordae were categorised to study the structures and mechanical properties.The constitutive equation was applied to fit the experimental stress-strain response of samples.The fitting parameters were utilized to simulate the mitral valve model.The microstructures of chordae and papillary muscles were analyzed quantitatively,which histologically revealed their macro-mechanical characteristics.The main research contents and conclusions are as follow:The chordae tendineae were classified according to valve leaflet types,including unstudied commissural chordae and the posterior intermediate chordae.The diameter and length of the chordae were measured,and the samples were tested by uniaxial tensile test under physiological mechanical load.The custom-made digital imaging calibration was established to track the gauge of markers as the strain of the samples.It showed that there are differences in the morphology of chordae when they were grouped by valve leaflets,but no distinction was witnessed in secant modulus under physiological conditions.The diameter of chord was significantly negatively correlated with the secant modulus at 5 MPa stress.Anatomical and morphological quantitative analysis of the anterior and posterior papillary muscles and the relative chordae were carried out.Biaxial tensile test was implemented for the stress-strain response in two directions of the papillary muscles.Uniaxial tensile test was utilized till samples rupture to capture stress-strain response of the chord.The results showed that there was no significant difference in mechanical properties between the anterolateral and posteromedial papillary muscles in circumferential and radial directions.The chord on the anterior papillary muscle side covered a larger area of the valve leaflets,and the posterior chordae had fewer numbers,but was longer than the anterior chordae and was stiffer under high stress.Three nonlinear constitutive equations and a Neo-Hookean equation were evaluated when it was used to fit the chordal experimental data of the physiological conditions.Appropriate equations were selected to fit the stress-strain response in the linear region of papillary muscle and related chord.Repeated verifications for stability of parameters were carried out by inducing random initial values.The mitral valve was scanned by micro CT and the model was reconstructed.Material properties were defined by the experimental data achieved in this study,and the mitral valve closure was simulated by finite element method.Study had demonstrated that the nonlinear equations fitting was better than linear fitting,and the Ogden equation showed the largest R~2 value.The experimental data of papillary muscle and chordae were fitted with simplified HO equation and Ogden equation respectively,and the parameters were proved stable.The valve leaflet closure was achieved during systole in the mitral valve computational simulation.Histological method was used to explore relationships between microstructures and macro-mechanical behaviors of chord.Sirius Red staining axial-sectional slices of chordal were made to observe collagen curve,and HE staining cross-sectional slices were made to count the number of blood vessels.Masson staining slices were used to measure the proportion of cross-sectional collagen cores on radial sections of chordae.Radial sections of chordal collagen fiber were observed by transmission electron microscope.Masson staining slices were performed on both sides of the papillary muscles in the circumferential and radial directions to observe the collagen content,the number of muscle cells and the collagen occupation.The results showed that there was no significant difference in the wavelength of the chordal collagen in each group,which may be confirmed by the similar mechanical properties under the physiological load.The number of chordal vessels in each group was different.The number of strut chord vessels was more than that of the other chord.Comparing with the chordae on anterior papillary muscle side,the chordae on the posterior papillary muscle side had a higher proportion of collagen core,higher density of collagen fiber and smaller diameter of fibril.The differences in microstructure may explain the higher tangent modulus of the chordae on posterior papillary muscle side.Masson staining slices of the papillary muscles on both sides in the circumferential and radial directions showed that the collagen contents,the number of muscle cells and the occupation proportion were similar,which might explain the different mechanical properties of the papillary muscles.In summary,this study confirmed that the morphology of the chordae grouped by valve leaflets was different,and there was no significant difference in mechanical properties under physiological load.The collagen crimp period of the chordae was similar,and the numbers of blood vessels in the chordal groups were different.Comparing with the chordae on anterior papillary muscle side,the tangent modulus under high stress of the chord on posterior papillary muscle was higher.The proportion of collagen core was higher,and the density of collagen fiber bundles was greater.No significant difference was noted in mechanical properties and microstructure of the anterior and posterior papillary muscles.Comparing with the linear equations,the non-linear constitutive equations demonstrated more accurate when fit chordal experimental data.The constitutive parameters of the chordae were proved feasible to simulate the proper coaptation of the mitral valve model.