Contribution of microtubule network to the passive anisotropic viscoelasticity of right ventricle free wall
Authors: LeBar Kristen , Roth Kellan , Evans Erith , Chicco Adam , Pang Jassia , Wang Zhijie 
Published: May 2023

Introduction: Microtubule (MT) polymerization is a key contributor to myocardium viscoelasticity and its contractile function. Arrangement of the MT network has been shown to impact myocyte viscoelasticity, according to prior studies on the 1D mechanics of isolated muscles [1,2]. However, the ventricular free wall is a complex, multi-layer tissue composed of myofibers, collagen and vasculature, and it exhibits anisotropic mechanical behavior. The role of MT in the entire tissue anisotropic viscoelasticity is unclear. Our aim is to investigate the contribution of MT to the passive, anisotropic viscoelasticity of healthy right ventricles (RVs). We hypothesize that MT hyper-polymerization alters tissue anisotropy and enhances viscosity more greatly than elasticity. Methods: All procedures and methods were approved by Colorado State University IACUC. Healthy, adult male Sprague Dawley rats (n=5) were euthanized, and the RV underwent equibiaxial stress-relaxation (ramp speed of 0.95 mm/s, strain of 6%) in intact state (baseline) and treated conditions to remove (via colchicine) and enhance (via deuterium oxide; D2O) MT polymerization. The longitudinal (L) direction was defined as the outflow tract direction. Viscoelastic parameters such as relaxation modulus and stored (elasticity) and dissipated (viscosity) energy were examined. Paired student t-test was performed and p<0.05 was considered significant. Results: The overall viscoelastic relaxation of RV was examined by relaxation modulus. As expected, MT hyper-polymerization increased the relaxation modulus, but the increase was only seen in the L direction (p<0.05). In contrast, MT de-polymerization led to the opposite effect or trend in the circumferential (C) direction (p<0.05). Similar changes were shown in the stored energy as an indicator of elasticity. The viscous response showed similar changes to the elastic response, as measured by dissipated energy (p<0.05). The viscosity was enhanced by MT hyper-polymerization in both directions (p<0.05), but it was not affected by MT de-polymerization. As a result, the ratio of dissipated energy to stored energy (V/E ratio) remained unchanged with reduced MT network, but it was increased in the C direction with enhanced MT network (p<0.05). Discussion: Our results showed that the healthy RV’s anisotropic viscoelasticity was differently affected by the removal and enhancement of MT network. There was no siginificant change in anisotropy or V/E ratio after the removal of the MT network. However, we observed an enhanced anisotropy and more elevation in viscosity compared to the increase in elasticity, as well as an increased V/E ratio after the enhancement of the MT network. As MT density is elevated in diseased RVs, our findings may provide novel insights into MT’s contribution to tissue viscoelasticity and physiological performance. References: [1] Cooper, G. Am. J. Physiol. Heart. Circ. Physiol., H1003-H1014, 2006. [2] Caporizzo, M.A. et. al, Nat. Rev. Cardiol., 364-378, 2022. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.