Multiscale Contrasts Between the Right and Left Ventricle Biomechanics in Healthy Adult Sheep and Translational Implications

Abstract

Cardiac biomechanics play a significant role in the progression of structural heart diseases (SHDs). SHDs alter baseline myocardial biomechanics leading to single or bi-ventricular dysfunction. But therapies for left ventricle (LV) failure patients do not always work well for right ventricle (RV) failure patients. This is partly because the basic knowledge of baseline contrasts between the RV and LV biomechanics remains elusive with limited discrepant findings. The aim of the study was to investigate the multiscale contrasts between LV and RV biomechanics in large animal species. We hypothesize that the adult healthy LV and RV have distinct passive anisotropic biomechanical properties. Ex vivo biaxial tests were performed in fresh sheep hearts. Histology and immunohistochemistry were performed to measure tissue collagen. The experimental data were then fitted to a Fung type model and a structurally informed model, separately. We found that the LV was stiffer in the longitudinal (outflow tract) than circumferential direction, whereas the RV showed the opposite anisotropic behavior. The anisotropic parameter K from the Fung type model accurately captured contrasting anisotropic behaviors in the LV and RV. When comparing the elasticity in the same direction, the LV was stiffer than the RV longitudinally and the RV was stiffer than the LV circumferentially, suggesting different filling patterns of these ventricles during diastole. Results from the structurally informed model suggest potentially stiffer collagen fibers in the LV than RV, demanding further investigation. Finally, type III collagen content was correlated with the low-strain elastic moduli in both ventricles. In summary, our findings provide fundamental biomechanical differences between the chambers. These results provide valuable insights for guiding cardiac tissue engineering and regenerative studies to implement chamber-specific matrix mechanics, which is particularly critical for identifying biomechanical mechanisms of diseases or mechanical regulation of therapeutic responses. In addition, our results serve as a benchmark for image-based inverse modeling technologies to non-invasively estimate myocardial properties in the RV and LV.

Keywords: Fung exponential strain energy function; anisotropy; collagen isoform; ovine; structurally informed model.

FIGURE 1

A representative image of the ovine heart with the labeling of the outflow (OT, longitudinal) direction for each ventricle.

FIGURE 2

Average equibiaxial stress-strain curves in the longitudinal (A) and circumferential (B) directions in the LV and RV (n = 7 per group). The shaded area is the standard error of the stress data, and the dash line is the standard error for the strain data.

FIGURE 3

(A,B) Elastic moduli (M) of LVs and RVs from the equibiaxial (A) and non-equibiaxial tests (B). (C,D) Strain-weighted elastic moduli (M/ε) of LVs and RVs from the equibiaxial (C) and non-equibiaxial tests (D). For the equibiaxial tests, n = 7 per group; for the non-equibiaxial tests, LV, L: n = 4; LV, (C) n = 5; RV, L: n = 7; RV, (C) n = 6. *: p < 0.05 comparison between the directions and p < 0.05 and p < 0.01 for comparison between the ventricles.

FIGURE 4

Simulated equibiaxial stress-strain curves generated by the four-parameter Fung model, using the average values of the fitting parameters for both ventricles in two directions.

FIGURE 5

(A) Longitudinal and circumferential zero-load elastic modulus M ₀ for each ventricle type, and (B) Anisotropic parameter K for each ventricle type. *: p < 0.05 comparison between the directions and p < 0.01 comparison between the ventricles, respectively.

FIGURE 6

Representative fitting results using the structurally informed model.

FIGURE 7

Histological measurement and correlation analysis for the collagen. (A) Variations in the content of collagen isoforms and the total collagen between the LV and RV, (B) Significant correlation between the type III collagen content and longitudinal M (M _L) at the low-strain range and (C) Significant correlation between the total collagen content and circumferential M/ε at the high-strain range.