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Abstract Right ventricular (RV) dysfunction is a major contributor to mortality in several cardiopulmonary diseases. However, the understanding of RV pathophysiology falls behind its left counterpart, limiting treatment options for conditions associated with discrete RV dysfunction and failure, such as pulmonary hypertension (PH). Accumulating evidence suggests that colchicine (COL) may have therapeutic benefits in multiple diseases, including PH. The mechanisms by which COL improves cardiovascular function are incompletely understood but may be associated with reductions in myocardial tissue viscoelasticity via microtubule depolymerization as demonstrated in prior ex vivo studies. The aim of this study is to investigate the impact of acute COL treatment on healthy and diseased RV organ function. Healthy and PH rats were anesthetized and catheterized for investigation of RV pressure-volume (PV) relationships before and after intramyocardial injections of COL. Marked RV failure was observed secondary to PH, characterized by elevated pulmonary vascular resistance (PVR), RV pressures, and end diastolic PV relation (EDPVR) with reduced RV compliance, preload and stroke volume. COL reversed pathological changes in parameters such as EDPVR, and improved RV preload, compliance, stroke volume and ejection fraction in PH rats. COL also reduced RV systolic pressure and heart rate in PH rats, which may be associated with broader effects of COL (improved PVR) in addition to myocardial viscoelastic reduction. In contrast, no significant effect on cardiopulmonary function was observed in healthy rats. These results highlight a potential contribution of RV viscoelasticity to ventricular dysfunction, implicating tissue viscoelasticity as a therapeutic target for RV failure patients. 

Abstract There is growing evidence of myocardial hysteresis and, recently, the viscoelasticity of healthy and pulmonary hypertensive (PH) right ventricle free walls (RVFW) has been studied by stress–relaxation. However, stress–relaxation does not fully capture thein vivodeformation of the tissue, and the changes in right ventricle hysteresis behavior with PH remain unknown. Our aim was to investigate RVFW biaxial hysteresis behavior with PH. We conducted equibiaxial cyclic sinusoidal tensile testing in healthy and PH rat RVFW tissues under 20% strain, with strain rates of 0.1&1 Hz (sub-physiological), and 5&8 Hz (physiological). Elastic modulus, loop height, stored and dissipated energies, the ratio of viscosity to elasticity (V/E), and the percentage of dissipated to total energy (damping) were derived. After PH, elastic modulus was elevated in both directions, while longitudinal loop height and stored and dissipated energies were increased (p< 0.05). Despite these individual changes in viscosity and elasticity, V/E ratio and damping were maintained. We further found frequency-dependent responses of V/E ratio and damping, and these were enhanced in the diseased RVs (p< 0.05 at 5&8 Hz) than healthy RVs (p< 0.05 only at 8 Hz). Finally, we observed significant correlations between individual mechanical properties and structural changes (collagen content/myofiber width), and the correlations were stronger in the longitudinal (p⩽ 0.006) than circumferential (p< 0.05) direction. Moreover, collagen had a much greater contribution (p⩽ 0.002) to tissue elasticity than myofiber (p⩽ 0.02). Multiple linear regression analyses revealed a significant role of myofibers, not collagen content, in the tissue viscosity in both directions (p< 0.05). Our results suggest the importance of incorporating tissue viscoelastic properties into pathophysiology as well as the design of cardiac biomimetic materials for advancements in cardiac health. 

Introduction:The right ventricle (RV) mechanical property is an important determinant of its function. However, compared to its elasticity, RV viscoelasticity is much less studied, and it remains unclear how pulmonary hypertension (PH) alters RV viscoelasticity. Our goal was to characterize the changes in RV free wall (RVFW) anisotropic viscoelastic properties with PH development and at varied heart rates. Methods:PH was induced in rats by monocrotaline treatment, and the RV function was quantified by echocardiography. After euthanasia, equibiaxial stress relaxation tests were performed on RVFWs from healthy and PH rats at various strain-rates and strain levels, which recapitulate physiological deformations at varied heart rates (at rest and under acute stress) and diastole phases (at early and late filling), respectively. Results and Discussion:We observed that PH increased RVFW viscoelasticity in both longitudinal (outflow tract) and circumferential directions. The tissue anisotropy was pronounced for the diseased RVs, not healthy RVs. We also examined the relative change of viscosity to elasticity by the damping capacity (ratio of dissipated energy to total energy), and we found that PH decreased RVFW damping capacity in both directions. The RV viscoelasticity was also differently altered from resting to acute stress conditions between the groups—the damping capacity was decreased only in the circumferential direction for healthy RVs, but it was reduced in both directions for diseased RVs. Lastly, we found some correlations between the damping capacity and RV function indices and there was no correlation between elasticity or viscosity and RV function. Thus, the RV damping capacity may be a better indicator of RV function than elasticity or viscosity alone. These novel findings on RV dynamic mechanical properties offer deeper insights into the role of RV biomechanics in the adaptation of RV to chronic pressure overload and acute stress.