# Translational Echocardiography: The Dog as a Clinical Research Model of Cardiac Dysfunction
## 5 (MDMV) Comparative Pathology and Pathophysiology  
The mitral valve structure undergoes severe and repeated mechanical stress during systole, the pressure generated by the contracting left ventricle causes the valve leaflets to close, resulting in mechanical stress on the valve structure. The fibroblasts and myofiboblasts in the valve tissue respond to this stress by synthesizing and remodeling the extracellular matrix, which is the network of proteins and other molecules that provide support and structure to the valve tissue. This remodeling process involves the deposition of new extracellular matrix components, such as collagen and elastin, and the breakdown of old or damaged components. During diastole, the pressure in the left atrium decreases, and the valve leaflets open, resulting in flexion of the valve structure. The smooth muscle cells and interstitial cells in the valve tissue respond to this mechanical stress by contracting and relaxing, respectively, to help maintain the valve's shape and function. Furthermore, the endothelial cells that line the inner surface of the valve leaflets experience shear stress from the blood flow. These cells respond to this stress by releasing signaling molecules that regulate cell behavior and extracellular matrix synthesis, helping to maintain the valve's integrity and function [30,31]. The above occurs when the heart valves open and close more than three billion times in the half-life of a human adult and more than half a billion times in the half-life of a canine. Figure 4: Myxomatous mitral valve degeneration in the canine patient’s left apical 4-chamber view. The mitral apparatus experiences the cardiac apparatus's most significant transvalvular pressure gradient [30]. During the contractile phase, the leaflets endure high degrees of tension and rapid mechanics of movement and stretching, constant tension, and, after complete closure, an extreme increase in tension and stiffness to avoid further deformation of the leaflets, and prevent the mitral regurgitation caused by the straightening of the collagen fibers within the leaflets [32; 33]. The macroscopic and histological structures of the human and canine leaflets are similar [34; 35] and are designed to withstand repeated stresses due to the specialized structure of the inner layers of the mitral leaflets [30; 34; 35]. The mitral valve is closely related to the fibrous skeleton of the heart, and the mitral annulus, in particular, is an important component of the fibrous skeleton that helps to maintain the shape and function of the valve [30; 36]. The valvular annulus is the ring-like structure that supports the mitral valve and connects it to the heart's muscular wall. It serves as an anchor for the valve's leaflets, chordae tendineae, and papillary muscles, allowing for the proper opening and closing of the valve during the cardiac cycle. The shape of the valvular annulus is not flat but rather saddle-shaped, with a higher curvature at the anterior and posterior ends and a lower curvature at the lateral ends. This shape reduces the stress on the chordae tendineae and leaflets during systole when the valve is closed, as it allows for the distribution of the mechanical forces evenly across the valve. The saddle-shaped annulus also enables the valve to open and close more efficiently, reducing the strain on the valve and its components [30; 37; 38]. Other similarities of the mitral valve structure in dogs and humans include the continuity of the anterior leaflet with the aortic valve cusps at the aortic root and a branched network of chordae tendineae that connects to the anterior and posterior papillary muscle [19]. The mitral apparatus, which is present in both humans and dogs, consists of layers of extracellular matrix and connective tissue. The specialized innermost regions include a spongy region made of an extracellular proteoglycan matrix and a fibrous region composed of collagen that extends to the chordae tendineae. Valvular interstitial cells are also present in the valve [30; 39; 40; 41].