Assessment of left ventricular mechanics in right ventricular overload using in silico rat models

Background To preserve cardiac function in overload conditions, the RV adapts by developing muscular hypertrophy through progressive tissue remodelling. This process may lead to a vicious cycle with detrimental effects on RV diastolic and systolic function, as seen in pulmonary arterial hypertension (PAH) patients [1]. However, how RV overload affects LV function and remodelling remains an open question [2]. Computational models of cardiac physiology offer an opportunity for investigating mechanisms difficult or impossible to analyse otherwise due to the existence of overlapping factors and technical limitations. Aim This study aims to assess the acute effects of RV overload and increased myocardial passive stiffness on the LV mechanical properties in an anatomically-based computational model of healthy rat heart. Methods A computational simulation pipeline of cardiac mechanics based on the Holzapfel-Ogden model has been implemented using MR images from a healthy rat. Whereas LV function was modelled realistically using catheter measurements conducted on the same subject than the MR imaging, RV function was based on representative literature values for healthy and PAH rats with RV overload. The following cases were defined (Fig. 1): CTRL, with normal RV function; PAH1, with 30% increase in RV ESV (end-systolic volume) and 15% increase in RV ESP (end-systolic pressure) in comparison to CTRL; and PAH2, with 60% increase in RV ESV and 30% increase in RV ESP compared to CTRL. The cardiac cycle was simulated for all cases whilst fitting the experimentally measured LV pressure and volume values from a healthy rat, which allowed quantifying the effects of RV overload on LV function. Results The increase of average circumferential strain in the LV correlated with the degree of RV overload simulated (CTRL: −8.7%, PAH1: −8.9%, PAH2: −9.2%), whilst average radial (CTRL: 35.2%, PAH1: 34.8%, PAH2: 30.3%) and longitudinal strains decreased (CTRL: −7.7%, PAH1: −7.4%, PAH2: −6.6%), as seen in Fig.2. However, regional differences in strain were significant: under RV overload conditions, circumferential strain increased in the septum (−3.5% difference in PAH2 vs. CTRL) but lower values were observed in the lateral wall (+1.7% difference in PAH2 vs. CTRL). Cardiac function of case PAH2 was simulated also with increased myocardial passive stiffness (2.67 kPa instead of 1.34 kPa) which presented a mild strain increase in the mid LV ventricle in comparison to PAH2 with normal stiffness (circumferential strain: −0.8%, radial strain: +0.5%, longitudinal strain: −0.2%). Conclusion Our study provides mechanistic evidence on how RV overload and increased passive myocardial stiffness causes a redistribution of strain and fibre stress in the LV, which may play a significant role in LV remodelling and function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): K.G. Jebsen Center for Cardiac Research Figure 1. Pressure – volume loops Figure 2. Mean mid-LV strains

Design and Compliant Control of a Piggyback Transfer Robot

Patient transfer, such as lifting and moving a bedridden patient from a bed to a wheelchair or a pedestal pan, is one of the most physically challenging tasks in nursing care. Although many transfer devices have been developed, they are rarely used because of the large time consumption in performing transfer tasks and the lack of safety and comfortableness. We developed a piggyback transfer robot that can conduct patient transfer by imitating the motion when a person holds another person on his/her back. The robot consisted of a chest holder that moves like a human back. In this paper, we present an active stiffness control approach for the motion control of the chest holder, combined with a passive cushion, for lifting a care-receiver comfortably. A human-robot dynamic model was built and a subjective evaluation was conducted to optimize the parameters of both the active stiffness control and the passive cushion of the chest holder. The test results of 10 subjects demonstrated that the robot could transfer a subject safely and the combination of active stiffness and passive stiffness were essential to a comfortable transfer. The objective evaluation demonstrated that an active stiffness of k= 4 kPa/mm along with a passive stiffness lower than the stiffness of human chest was helpful for a comfort feeling.

Age-related increase in muscle stiffness is muscle length dependent and associated with muscle force in senior females

Background In aging, muscle stiffness is considered as one of the factors associated with the reduction of force generation capability. There have been inconsistent findings on age-related alteration in the passive stiffness of quadriceps muscle in the female adults. Thus, the aim of this study was to determine the effect of aging on the shear moduli of the superficial muscle heads of the quadriceps and to explore its relationship with knee extension force. Methods Passive shear moduli of the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) were measured at rest using shear wave elastography in 20 young and 20 senior female adults. Measurements were repeated at four knee joint positions, that is, 30°, 60°, 90°, and 105° of knee flexion. Maximal isometric voluntary knee extension force was assessed at 30°, 60°, and 90° of knee flexion. Results As per our findings, senior adults were determined to have significantly higher passive muscle shear moduli in the RF (by 34% – 68%; all p < 0.05) and the VL muscle heads (by 13%–16%, all p < 0.05) at and beyond 60° of knee flexion. Age-related increase in the VM was evident at 105° knee flexion (by11%, p = 0.020). The RF shear modulus was negatively correlated to the maximal isometric voluntary contraction force measured at 60° (r = − 0.485, p = 0.030) in senior adults. Conclusions Senior female adults had greater passive stiffness at the superficial muscle heads of the quadriceps muscles when measured at long muscle length. Among the senior female adults, the passive stiffness of RF has been determined to have a negative association with the knee extensor force only at 60° knee flexion. No significant association was noted for other angles and muscles.

Sex Differences in the Mechanical and Neurophysiological Response to Roller Massage of the Plantar Flexors

Self-massage using foam rollers, sticks, or balls has become a popular technique to enhance joint range of motion (ROM). Although increases are reported to be larger in females than males, the mechanisms of this observation are unclear. The present study aimed to investigate the effect of roller massage (RM) on ROM, passive tissue stiffness, and neurophysiological markers as a function of sex. Males (n = 15, 22.8 ± 2.9 yrs.) and females (n = 14, 21.1 ± 0.7 yrs.) performed three 60-second bouts of calf RM. Outcomes assessed pre-, and post-intervention included passive dorsiflexion (DF) ROM, passive tissue stiffness, passive torque, DF angle at the first stretch sensation, shear elastic modulus, and spinal excitability. DF ROM (+35.9 %), passive torque at DF ROM (+46.4 %), DF angle at first stretch sensation (+32.9 %), and pain pressure threshold (+25.2 %) increased in both groups (p<.05) with no differences between males and females (p > 0.05). No changes were observed for passive stiffness, shear elastic modulus, and spinal excitability (p > 0.05). Roller massage may increase ROM independently of sex, which, in the present study, could not be ascribed to alterations in passive stiffness or neurophysiological markers. Future studies may further elucidate the role of sensory alterations as possible factors driving RM-induced changes in flexibility.

Elasticity of the Achilles Tendon in Individuals With and Without Plantar Fasciitis: A Shear Wave Elastography Study

The elastic properties of the Achilles tendon (AT) are altered in local injury or other diseases and in response to changes in mechanical load. Recently, elastography has been used to evaluate variations in tendon elastic properties, mainly among healthy individuals or athletes. Therefore, this study evaluated the biomechanical changes in ATs in individuals with and without plantar fasciitis (PF). The purposes were as follows: (1) to evaluate the passive stiffness of three regions of the AT which defined as 0 (AT0 cm), 3 (AT3 cm), and 6 cm (AT6 cm) above the calcaneal tuberosity in participants with and without PF, (2) to investigate the interplay between the passive stiffness in patients with PF and pain, (3) to detect optimal cut-off points of stiffness of the AT in assessing individuals with chronic PF, and (4) to determine the correlation between the plantar fascia thickness (PFT) and pain. This cross-sectional study included 40 participants (mean age = 51 ± 13 years). When the ankle was in a relaxed position, patients with PF experienced increased passive stiffness in AT0 cm (p = 0.006) and AT3 cm (P = 0.003), but not in the neutral position. Significant correlations were observed between pain and stiffness of AT (AT0 cm r = 0.489, P = 0.029; AT3 cm r = 487, P = 0.030; AT6 cm r = 0.471, P = 0.036), but not in the PFT (P = 0.557). Optimal cut-off stiffness was AT (452 kPa) in the relaxed ankle position. The plantar fascia of patients with PF was significantly thicker than that of the controls (P &lt; 0.001). Findings from the present study demonstrate that tendon stiffness is a good indicator of the clinical situation of patients with PF. Monitoring passive tendon stiffness may provide additional information to assess severity of the condition and guide therapeutic. The treatment programs for PF should also be tailored to the distal AT, as conventional therapy might not be targeted to tight tendons.

Interventricular Differences of Signaling Pathways-Mediated Regulation of Cardiomyocyte Function in Response to High Oxidative Stress in the Post-Ischemic Failing Rat Heart

Standard heart failure (HF) therapies have failed to improve cardiac function or survival in HF patients with right ventricular (RV) dysfunction suggesting a divergence in the molecular mechanisms of RV vs. left ventricular (LV) failure. Here we aimed to investigate interventricular differences in sarcomeric regulation and function in experimental myocardial infarction (MI)-induced HF with reduced LV ejection fraction (HFrEF). MI was induced by LAD ligation in Sprague–Dawley male rats. Sham-operated animals served as controls. Eight weeks after intervention, post-ischemic HFrEF and Sham animals were euthanized. Heart tissue samples were deep-frozen stored (n = 3–5 heart/group) for ELISA, kinase activity assays, passive stiffness and Ca2+-sensitivity measurements on isolated cardiomyocytes, phospho-specific Western blot, and PAGE of contractile proteins, as well as for collagen gene expressions. Markers of oxidative stress and inflammation showed interventricular differences in post-ischemic rats: TGF-β1, lipid peroxidation, and 3-nitrotyrosine levels were higher in the LV than RV, while hydrogen peroxide, VCAM-1, TNFα, and TGF-β1 were increased in both ventricles. In addition, nitric oxide (NO) level was significantly decreased, while FN-1 level was significantly increased only in the LV, but both were unchanged in RV. CaMKII activity showed an 81.6% increase in the LV, in contrast to a 38.6% decrease in the RV of HFrEF rats. Cardiomyocyte passive stiffness was higher in the HFrEF compared to the Sham group as evident from significantly steeper Fpassive vs. sarcomere length relationships. In vitro treatment with CaMKIIδ, however, restored cardiomyocyte passive stiffness only in the HFrEF RV, but had no effect in the HFrEF LV. PKG activity was lower in both ventricles in the HFrEF compared to the Sham group. In vitro PKG administration decreased HFrEF cardiomyocyte passive stiffness; however, the effect was more pronounced in the HFrEF LV than HFrEF RV. In line with this, we observed distinct changes of titin site-specific phosphorylation in the RV vs. LV of post-ischemic rats, which may explain divergent cardiomyocyte stiffness modulation observed. Finally, Ca2+-sensitivity of RV cardiomyocytes was unchanged, while LV cardiomyocytes showed increased Ca2+-sensitivity in the HFrEF group. This could be explained by decreased Ser-282 phosphorylation of cMyBP-C by 44.5% in the RV, but without any alteration in the LV, while Ser-23/24 phosphorylation of cTnI was decreased in both ventricles in the HFrEF vs. the Sham group. Our data pointed to distinct signaling pathways-mediated phosphorylations of sarcomeric proteins for the RV and LV of the post-ischemic failing rat heart. These results implicate divergent responses for oxidative stress and open a new avenue in targeting the RV independently of the LV.

Hybrid Parallel Compliance Allows Robots to Operate With Sensorimotor Delays and Low Control Frequencies

Animals locomote robustly and agile, albeit significant sensorimotor delays of their nervous system and the harsh loading conditions resulting from repeated, high-frequent impacts. The engineered sensorimotor control in legged robots is implemented with high control frequencies, often in the kilohertz range. Consequently, robot sensors and actuators can be polled within a few milliseconds. However, especially at harsh impacts with unknown touch-down timing, controllers of legged robots can become unstable, while animals are seemingly not affected. We examine this discrepancy and suggest and implement a hybrid system consisting of a parallel compliant leg joint with varying amounts of passive stiffness and a virtual leg length controller. We present systematic experiments both in computer simulation and robot hardware. Our system shows previously unseen robustness, in the presence of sensorimotor delays up to 60 ms, or control frequencies as low as 20 Hz, for a drop landing task from 1.3 leg lengths high and with a compliance ratio (fraction of physical stiffness of the sum of virtual and physical stiffness) of 0.7. In computer simulations, we report successful drop-landings from 3.8 leg lengths (1.2 m) for a 2 kg quadruped robot with 100 Hz control frequency and a sensorimotor delay of 35 ms.