The interventricular septum contributes to the pumping function of both ventricles. However, unlike the ventricular wall, its mechanical behavior remains largely unknown. To fill the knowledge gap, this study aims to characterize the biaxial and transmural variation of the mechanical properties of the septum and compare it to the free walls of the left and right ventricles (LV/RV). Fresh hearts were obtained from healthy, adult sheep. The septal wall was sliced along the mid-line into two septal sides and compared to the epicardial layers of the LV- and RV-free walls. Biaxial tensile mechanical tests and constitutive modeling were performed to obtain the passive mechanical properties of the LV- and RV-side of the septum and ventricular walls. We found that both sides of the septum were significantly softer than the respective ventricular walls, and that the septum presented significantly less collagen than the ventricular walls. At low strains, we observed the symmetric distribution of the fiber orientations and a similar anisotropic behavior between the LV-side and RV-side of the septum, with a stiffer material property in the longitudinal direction, rather than the circumferential direction. At high strains, both sides showed isotropic behavior. Both septal sides had similar intrinsic elasticity, as evidenced by experimental data and constitutive modeling. These new findings offer important knowledge of the biomechanics of the septum wall, which may deepen the understanding of heart physiology.
The extracellular matrix (ECM) forms a mesh surrounding tissue, made up of fibrous and non-fibrous proteins that contribute to the cellular function, mechanical properties of the tissue and physiological function of the organ. The cardiac ECM remodels in response to mechanical alterations (e.g., pressure overload, volume overload) or injuries (e.g., myocardial infarction, bacterial infection), which further leads to mechanical and functional changes of the heart. Collagen, the most prevalent ECM protein in the body, contributes significantly to the mechanical behavior of myocardium during disease progression. Alterations in collagen fiber morphology and alignment, isoform, and cross-linking occur during the progression of various cardiac diseases. Acute or compensatory remodeling of cardiac ECM maintains normal cardiac function. However, chronic or decompensatory remodeling eventually results in heart failure, and the exact mechanism of transition into maladaptation remains unclear. This review aims to summarize the primary role of collagen accumulation (fibrosis) in heart failure progression, with a focus on its effects on myocardial tissue mechanical properties and cellular and organ functions.
Cardiac biomechanics play a significant role in the progression of structural heart diseases (SHDs). SHDs alter baseline myocardial biomechanics leading to single or bi-ventricular dysfunction. But therapies for left ventricle (LV) failure patients do not always work well for right ventricle (RV) failure patients. This is partly because the basic knowledge of baseline contrasts between the RV and LV biomechanics remains elusive with limited discrepant findings. The aim of the study was to investigate the multiscale contrasts between LV and RV biomechanics in large animal species. We hypothesize that the adult healthy LV and RV have distinct passive anisotropic biomechanical properties. Ex vivo biaxial tests were performed in fresh sheep hearts. Histology and immunohistochemistry were performed to measure tissue collagen. The experimental data were then fitted to a Fung type model and a structurally informed model, separately. We found that the LV was stiffer in the longitudinal (outflow tract) than circumferential direction, whereas the RV showed the opposite anisotropic behavior. The anisotropic parameter K from the Fung type model accurately captured contrasting anisotropic behaviors in the LV and RV. When comparing the elasticity in the same direction, the LV was stiffer than the RV longitudinally and the RV was stiffer than the LV circumferentially, suggesting different filling patterns of these ventricles during diastole. Results from the structurally informed model suggest potentially stiffer collagen fibers in the LV than RV, demanding further investigation. Finally, type III collagen content was correlated with the low-strain elastic moduli in both ventricles. In summary, our findings provide fundamental biomechanical differences between the chambers. These results provide valuable insights for guiding cardiac tissue engineering and regenerative studies to implement chamber-specific matrix mechanics, which is particularly critical for identifying biomechanical mechanisms of diseases or mechanical regulation of therapeutic responses. In addition, our results serve as a benchmark for image-based inverse modeling technologies to non-invasively estimate myocardial properties in the RV and LV.
Introduction Myocardium stiffening is well known in heart failure (HF) development, and it contributes to cardiac dysfunction. Myocardium is viscoelastic, which means that both elastic and viscous resistance exist under dynamic loading. There are limited studies of myocardium viscoelasticity, particularly for the right ventricle (RV). Because viscoelasticity is a time‐ and strain‐dependent mechanical behavior, the measurement at physiological rates & non‐linear deformation is critical. This study aims to develop a high‐speed biaxial tester that induces physiological deformation to characterize RV viscoelasticity in rats. Methods To enable the viscoelasticity measurement at physiological conditions, we built a biaxial tester that induces non‐linear, cyclic stretch of myocardium at rodent heart rates. Biaxial sinusoidal stretches were induced by actuators (1400mm/s) (Zaber), forces were recorded by load cells (Honeywell) at 1 kHz, and strains were obtained by a high‐speed camera (Baumer) at up to 200 fps. The LabVIEW and MATLAB codes were developed for performing biaxial tests at various frequencies with synchronized force and image data acquisition. To validate the biaxial tester, isotropic polydimethylsiloxane (PDMS) was used due to its similar viscoelasticity to cardiovascular tissues. PDMS sheets were prepared (Sylgard 184) for equibiaxial tests. Then, consistency between different axes’ measurements, synchronization of the axes’ movement, and accurate viscoelastic measurement were evaluated. Next, we performed equibiaxial cyclic sinusoidal tests on healthy rat RVs. After euthanasia, RV free wall was dissected and mounted. The outflow track direction was defined as the longitudinal direction. The RV was placed in a relaxant solution prior to testing, then preloaded by ~0.1 N and preconditioned by 15 cycles. Stress‐strain loops were derived for viscoelastic analysis. Results First, we examined if the biaxial tester could achieve planar biaxial tests at desired frequencies. The equibiaxial data obtained from PDMS sheets showed that the tester induced cyclic sinusoidal stretch at various frequencies up to 8 Hz (Fig. 1a), and the viscoelastic behavior measured at two axes were very close (Fig. 1b), thus confirming the tester’s accurate biaxial measurement of the isotropic material. The PDMS clearly showed frequency‐dependent changes in the hysteresis loops (Fig. 1c), with trends of increasing elasticity (slope of loop) and viscosity (area of loop) at higher frequencies. We further derived the viscosity by measuring Tan(δ) (Fig. 1d). The frequency‐dependent elasticity and viscosity of the PDMS sheet were consistent with literature data. Next, we obtained preliminary viscoelasticity data of healthy rat RVs (at 0.1‐2 Hz). Our data showed strain‐rate dependent changes in the hysteresis loops (Fig. 2). The dissipated energy (loop area) as well as the stiffness (loop slope) of the RV tended to increase with increasing frequency. The RV tissue showed similar viscoelastic behavior in both directions at all frequencies. Con...
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.
Introduction Right ventricle failure (RVF) secondary to pulmonary hypertension (PH) is a key risk factor for PH patients. The RV mechanical behavior is an important determinant of its function. However, compared to the nonlinear anisotropic elasticity, it remains unclear how RV biaxial viscoelasticity alters with PH. Our goal is to characterize the changes in RV biaxial viscoelasticity at rest and exercise conditions in response to PH. We hypothesize that PH alters RV anisotropy, viscoelasticity type and the response to exercised heart rate. Methods All procedures were approved by Colorado State University IACUC. Briefly, adult male rats were treated by monocrotaline (MCT, 60 mg/kg) for 3 weeks to induce PH. Healthy rats were used as controls (CTL). After euthanasia, ex vivo equibiaxial stress relaxation tests were performed to quantify the RV viscoelasticity. The outflow track direction was defined as the longitudinal direction. Two sets of stress relaxation tests were included: 1) Using different strain levels (3‐15%) at three fixed ramp speeds (2, 5 and 8 Hz); and 2) using different ramp speeds (0.1‐8 Hz) mimicking non‐physiological and physiological heart rates at rest and exercise at a fixed strain level (20%). The relaxation modulus and the normalized stress were used to indicate the RV viscoelasticity. The logarithmic scale plot from the first set data was used to analyze the type of RV viscoelasticity. A student’s t‐test was performed and p<.05 was treated as significant. Results The establishment of RVF was confirmed by echocardiography. As shown in Fig. 1, we observed frequency‐dependent viscoelasticity in both groups and directions, except for the elasticity of CTL RV in C direction. PH development led to more significant increase in viscoelasticity in L direction compared to the C direction (Fig. 1). The examination of the viscoelasticity at physiological strain‐rates showed that compared to the CTL RV, the MCT RV 1) became anisotropic in elasticity and stiffer in the L direction (Fig. 2A); 2) had increased viscosity in the L direction (Fig. 2B); and 3) had reduced viscoelasticity from the rest to exercise states (Fig. 2). Our results suggested that during exercise, the healthy RV’s viscoelastic behavior was maintained, whereas the diseased RV had decreased viscoelasticity. Finally, we found that the CTL RV was quasi‐linear viscoelastic at all testing frequencies, whereas the MCT RV was nonlinear viscoelastic in all testing conditions, except for the L behavior at sub‐physiological frequency. Therefore, PH changed the RV viscoelasticity from a quasi‐linear to fully nonlinear type. Conclusion This is the first report of RV biaxial viscoelasticity changes with PH in rats. In the diseased RV, increased viscoelasticity and altered anisotropy and viscoelasticity type were observed, and the viscoelasticity was reduced during exercise. These novel findings improve our understanding of RV biomechanics in response to pulsatile mechanical loadings at rest and exercise conditions.
Background The myocardium is viscoelastic, which means there exists elastic and viscous resistant forces during cardiac motion. It has been shown that cardiomyocyte (CM) or muscle fiber has significant viscoelasticity, and microtubule depolymerization via colchicine treatment reduces the CM’s viscoelasticity. However, most prior study is focused on the left ventricle, and the role of CM in right ventricle (RV) viscoelasticity in healthy and pulmonary hypertensive (PH) states is poorly understood. Our goal is to evaluate the contribution of CM to RV viscoelasticity in healthy and PH rats. We hypothesize that CM contributes to both healthy and PH RV viscoelasticity. Methods All procedures were approved by Colorado State University IACUC. 6‐week‐old male rats were treated with 3‐week monocrotaline (MCT) (60 mg/kg) to induce PH, and intact healthy rats served as control. RV function was quantified by echocardiography and in vivo pressure‐volume (PV) measurements. After euthanasia, RV free wall underwent equibiaxial stress relaxation in a relaxant bath to obtain passive, biaxial viscoelasticity pre and post colchicine treatment (0.3mM). The tissue was stretched at 20% of strain and with physiological ramp speed (5Hz). Relaxation modulus and normalized stress at 0.01 s were used to quantify elasticity and viscosity. Student t test was performed. Results In vivo RV function measurements showed the development of PH and RV failure in MCT rats (Table 1). Marked RV dilation and decreased fractional shortening confirmed the RV failure establishment. PV loop data with fewer samples (n=3) also implies declines in cardiac output, contractility (Ees) and ventricular‐vascular coupling (Ees/Ea). At the baseline, PH development led to increased viscoelasticity in the RV (Fig. 1). Mechanical data before and after colchicine treatment showed reduced elasticity in both healthy and MCT RVs (Fig. 1A&B). The percentage reduction in elasticity was similar between groups, indicating a similar contribution of CM to RV elasticity. Unexpectedly, we did not observe significant change in viscosity after colchicine treatment in both groups (Fig. 1C&D). Moreover, the control RVs were isotropic, whereas the MCT RVs showed marked anisotropy in elasticity (Fig. 1B). Conclusion Our results demonstrated similar impact of CM on RV viscoelasticity before and after PH development, despite the CM hypertrophy. Colchicine reduced elasticity in healthy and MCT RVs, but minimally changed RV viscosity. These findings will deepen the understanding of biomechanical mechanism of RV failure associated with viscoelastic changes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.