Myocardial remodeling takes a closer look at adaptations to elevated stress
Myocardial remodeling takes a closer look at adaptations to elevated stress lead image
Pulmonary arterial hypertension (PAH) creates a pressure-induced stress on the right ventricle (RV) and can lead to mechanical heart failure. This elevated stress does not go unnoticed by the myocardial cells. The increased pressure on the right ventricular free wall (RVFW) leads to mechanical and structural remodeling of heart cells.
Research reported in APL Bioengineering uses modeling to extrapolate the mechanisms of myocardial cell remodeling in response to PAH. The pressure increase leads to the development of denser and more fibrous connective tissue in the mid-wall region of the RVFW. Constitutive modeling allowed for the analysis of how the heart tissue fibers alter in disease, including how they interact with each other, providing a platform for assessing potential therapeutic interventions for PAH.
Histologically stained sections of rat heart specimens provided quantified measurements of orientation distributions as well as myofibers’ and collagen fibers’ volume fractions across the organ wall. The authors also measured changes in the mechanical behaviors of the RVFW tissue, and used the collection of data to create a representative mathematical model for predicting RVFW myocardium tissue behaviors.
Results for PAH samples showed stress-strain behaviors with intense stiffening in the longitudinal direction (heart apex to outflow). The stiffening was a direct result of localized fiber-level adaptations in the RVFW mid-wall region to accommodate mechanical loading during passive ventricle inflation. Moreover, the mechanical coupling between the myofibers and collagen fibers was enhanced in the PAH specimens.
This research represents the first attempt to comprehend remodeling from PAH by integrating a cellular tissue-organ analysis. “Moving forward, to gain a complete understanding of the heart, we are currently looking at how both ventricles of the heart alter under PAH, using this tissue-level model,” said Sacks, an author of the paper.
Source: “Transmural remodeling of right ventricular myocardium in response to pulmonary arterial hypertension,” by Reza Avazmohammadi, Michael Hill, Marc Simon, and Michael Sacks, APL Bioengineering (2017). The article can be accessed at https://doi.org/10.1063/1.5011639 .
