Stress relaxation behavior of left ventricular myocardium in mice

Abstract

BackgroundMyocardial tissues are known to exhibit viscoelastic behavior, i.e., the myocardial wall stress is gradually decaying when stretched at a constant level, referred to as stress relaxation behavior. The study of this behavior becomes important in structural heart diseases, where both passive and active relaxation behaviors of the myocardium may alter. As myocardial tissues display a complex, 3D micro‐architecture, the anisotropy of stress relaxation remains understudied. Our objective in this study was to investigate the anisotropy of (passive) stress relaxation behavior of the left ventricular (LV) myocardium in healthy small animals.MethodsWe used biaxial stress relaxation tests in wild‐type murine specimens (n=2). Full‐thickness myocardium LV free wall (LVFW) specimens were isolated from the mouse hearts (Fig. 1a), with the slab edges being aligned with the longitudinal (apex‐to‐outflow‐tract), circumferential, and radial directions of the LV. The specimens were mounted in a biaxial mechanical testing machine along the circumferential and longitudinal directions. The specimens were stretched in three different loading protocols with circumferential‐to‐longitudinal strain ratios of 30:30, 15:30, and 30:15%. The samples were loaded to the peak strain at a rate of 0.01 s‐1 and held at this stretch for 10 minutes to allow the relaxation. The time‐varying stress was recorded. We used an exponential decay fit to estimate the stress relaxation time constants in both directions.ResultsStress relaxation time constants showed noticeable differences between multiple loading ratios with equibiaxial loading (30:30) having the largest relaxation time constant followed by the circumferential stress in the 30:15 ratio (Fig. 1b). The larger strains led to larger stress relaxation constants (Fig. 1b‐c) indicating a strain‐dependent viscoelastic behavior. The quasi‐static equibiaxial loading of the same specimens resulted in a nearly isotropic behavior (not shown here), exhibiting insignificant contrast between the stresses in the circumferential and longitudinal directions. Interestingly, the contrast in the relaxation behavior between the circumferential and longitudinal directions were similarly insignificant (Fig. 1b). Non‐equibiaxial loadings (15:30 and 13:50) showed significantly faster relaxation for the direction with smaller strains (Fig. 1b).ConclusionsMyocardial tissue viscoelasticity is an important behavior contributing to both diastolic and systolic cardiac function, which remains understudied, especially in case of structural heart diseases associated with impaired relaxation in the LV. Our study suggests that stress relaxation behavior is prominent in the LV myocardium and may exhibit different relaxation behavior depending on strain magnitudes and strain ratios along different directions. The level of anisotropy in stress relaxation was found to be similar to the level of anisotropy in the tissue quasi‐static behavior. These results serve to motivate further studies to fully characterize the viscoelastic behavior of LV myocardium and its contribution to the LV relaxation and filling in murine models of LV diseases.