Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Monday Speaker Abstracts

MULTISCALE MODEL PREDICTIONS OF HEART GROWTH APPLIED TO POSTPARTUM AND HYPERTENSIVE PREGNANCIES Molly Kaissar 1 ; Kyoko Yoshida ; 1 University of Minnesota - Twin Cities, Biomedical Engineering, Minneapolis, MN, USA Pregnancy stands at the interface of mechanics and biology. The growing fetus combined with a surge in circulating hormones induce rapid growth and remodeling of the maternal cardiovascular system. We previously developed a multiscale computational model that incorporates hormonal and hemodynamic changes during pregnancy to successfully predict left ventricular (LV) growth in rats. Here, we assess our model’s ability to predict heart growth after delivery and in hypertensive pregnancies. Our multiscale model couples a cell-signaling model that predicts cardiomyocyte hypertrophy in response to reproductive and cardiovascular hormones, as well as a mechanotransduction pathway, to a mechanics-based model of the rat heart and circulation that predicts organ-level LV growth in response to hemodynamic changes. We simulated 21 days of pregnancy, followed by 21 days of postpartum changes in hemodynamics and hormones. We investigated both non-lactating and lactating rats, since they exhibit differences in postpartum hormones and hemodynamics. In addition, we simulated three cases of pregnancy with superimposed hypertension: Angiotensin II infusion (+AngII), transverse aortic constriction (+TAC), and reduced uterine perfusion pressure (+RUPP). Our model predicted LV mass decrease in non-lactating rats, while the elevated hormones and cardiac output led to LV mass increase in lactating rats, consistent with the available literature. Our hypertension simulations correctly captured LV growth in +AngII and +TAC during pregnancy but could not capture reported growth in the +RUPP group. Discussion: Our multiscale model correctly captured cardiac growth during postpartum and in 2 of 3 cases of hypertensive pregnancies. Our analysis indicates a key hormonal role in cardiac growth during hypertensive pregnancies. In contrast, our model indicated dynamic mechanical signals on cardiomyocytes during postpartum, suggesting a key mechanical role in driving heart growth after delivery. We are currently improving our model to include other key hormones to improve our predictions, specifically for +RUPP pregnancies.

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