Investigations of the Microstructural and Mechanical Properties of the Four Heart Valves

Abstract

The four heart valves (HVs) regulate the unidirectional flow of blood throughout the four chambers of the heart. The artioventricular heart valves (AHVs) enforce this unidirectional flow between each atrium and the respective ventricle, while the semilunar heart valves (SHVs) governs the flow of blood from the ventricles into the major arteries. The ability to maintain this one directional flow during the cardiac cycle is governed by the collagenous leaflets (or cusps) that prevent retrograde blood flow. Dysfunction of the leaflet microstructure (e.g., stenosis) or failure of sub-valvular components can affect the mechanical properties of these tissues, negating complete coaptation and resulting in valvular regurgitation. Clinical therapeutics for heart valve regurgitation vary from native valve repair to implementation of mechanical or bioprosthetic heart valve, both of which exhibit limitations for long-term prevention of regurgitation. Understanding the relationship between the collagen microstructure and tissue mechanics of these heart valve leaflets will not only elucidate the underlying pathology, but also provide the constitutive relations necessary to inform multiscale computational models for improving the treatment of HV disease. To further examine the microstructural and mechanical properties of the HV leaflets, this thesis research employed a polarization-based opto-mechanical system, capable of quantifying the realignment and reorientation of the tissue’s underlying collagen fiber architecture (CFA) when subjected to varying biaxial mechanical loads. Biaxial testing revealed a J-shaped stress-strain relationship for all HV leaflets, with greater extensibility in the tissue’s radial direction than the circumferential direction under all biaxial testing protocols. We also observed the SHVs to be more extensible than the AHVs in the radial direction, and variations in the mechanical response contingent on anatomical position (i.e., left/right side of heart). For example, the tricuspid and pulmonary valve leaflets were more extensible in the radial direction than their left heart counterparts, the mitral and aortic valve. Our collagen microstructure quantifications showed a loading-dependent and spatially-varied CFA for all HV leaflets. Further, under equibiaxial loading, the collagen fibers were better aligned and were preferentially oriented towards the circumferential axis. Under non-equibiaxial loading, however, the CFA displayed reorientation towards the direction of the greatest applied loading. The AHVs exhibited the greatest collagen fiber alignment under increased loading, while the SHVs were more susceptible to CFA reorientation, pointing towards the variations in physiological loading environment. Findings for the four HVs provide a microstructural basis for the observed mechanical behavior, and elucidate the differences in anatomical position and function. In summary, these investigations further elucidate the microstructure-mechanical relationship in HV leaflets, which is essential for developing multiscale models and refining clinical therapeutics.