Computational modeling of cardiac growth in the post-natal rat with a strain-based growth law

Abstract

Introduction: The postnatal heart grows mostly in response to increased hemodynamic load. However, the specific biomechanical stimuli that stimulate cardiac growth as a reaction to increased hemodynamic load are still poorly understood. It has been shown that isolated neonatal rat cardiac myocytes normalize resting sarcomere length by adding sarcomeres in series when subjected to uniaxial static strain. Because there is experimental evidence that myocytes can distinguish the direction of stretch, it was postulated that myocytes also may normalize interfilament lattice spacing as a response to cross-fiber stretch.

Methods: A growth law was proposed in which fiber axial growth was stimulated by fiber strain deviating from zero and fiber radial growth by cross-fiber strain (parallel to the wall surface) deviating from zero. Fiber radial growth rate constant was 1/3 of the fiber axial growth rate constant. The growth law was implemented in a finite element model of the newborn Sprague-Dawley rat residually stressed left ventricle (LV). The LV was subjected to an end-diastolic pressure of 1 kPa and about 25 weeks of normal growth was simulated.

Results: Most cellular and chamber dimension changes in the model matched experimentally measured ones: LV cavity and wall volume increased from 2.3 and 54 μl, respectively, in the newborn to 276 μl and 1.1 ml, respectively, in the adult rat; LV shape became more spherical; internal LV radius increased faster than wall thickness; and unloaded sarcomere lengths exhibited a transmural gradient. The major discrepancy with experiments included a reversed transmural gradient of cell length in the older rat.

Conclusion: A novel strain-based growth law has been presented that reproduced physiological postnatal growth in the rat LV.