Performance criteria for optimization of cardiac assistance

A performance criterion and weighting factors for the optimal cardiac assistance are investigated by applying Tellegen's network theorem and tolerance analysis on animal experimental data for left ventricular (LV) bypass on the failing heart. Two major factors with respect to cardiac assistance (total power delivered to the peripheral circulatory system, and changes in temporal pattern of ventricular contraction) are represented by two performance criteria,J ₁ andJ ₂ whereJ ₁ relates to the sum of LV and pump power, andJ ₂ relates to the “peakedness” factor of LV power. The total performance index (J) is determined as the weighted sum ofJ ₁ andJ ₂;J=w ₁J₁+w₂J₂. The weighting factors,w ₁ andw ₂, are computed as inverses of the tolerance in the performance contours with respect to improvement of stroke work per minute from pre- to post-bypass condition.     

An efficient robotic tendon for gait assistance

A robotic tendon is a spring based, linear actuator in which the stiffness of the spring is crucial for its successful use in a lightweight, energy efficient, powered ankle orthosis. Like its human analog, the robotic tendon uses its inherent elastic nature to reduce both peak power and energy requirements for its motor. In the ideal example, peak power required of the motor for ankle gait is reduced from 250 W to just 77 W. In addition, ideal energy requirements are reduced from nearly 36 J to just 21 J. Using this approach, an initial prototype has provided 100% of the power and energy necessary for ankle gait in a compact 0.95 kg package, seven times less than an equivalent motor/gearbox system.     

Dynamic optimization of in-series cardiac assistance by means of intra-aortic balloon pumping

Analytical techniques are developed which permit objective control of asiist device driving systems. In addition to being objective, the techniques described in this paper are optimal in the sense of minimizing a performance index which consists of a term involving left ventricular power and a term involving deviations of aorta hemodynamic parameters from normal values. Comparisons are included of off-line computations and measurements on dogs with experimentally induced myocardial infarctions undergoing intraaortic balloon pumping.     

Modelling the mechanical properties of cardiac muscle

A model of passive and active cardiac muscle mechanics is presented, suitable for use in continuum mechanics models of the whole heart. The model is based on an extensive review of experimental data from a variety of preparations (intact trabeculae, skinned fibres and myofibrils) and species (mainly rat and ferret) at temperatures from 20 to 27°C. Experimental tests include isometric tension development, isotonic loading, quick-release/restretch, length step and sinusoidal perturbations. We show that all of these experiments can be interpreted with a four state variable model which includes (i) the passive elasticity of myocardial tissue, (ii) the rapid binding of Ca²⁺ to troponin C and its slower tension-dependent release, (iii) the kinetics of tropomyosin movement and availability of crossbridge binding sites and the length dependence of this process and (iv) the kinetics of crossbridge tension development under perturbations of myofilament length.     

Molecular aspects of mechanical stress-induced cardiac hypertrophy

To elucidate the signal transduction pathway from external stimuli to nuclear gene expression in mechanical stress-induced cardiac hypertrophy, we examined the time course of activation of protein kinases such as Raf-1 kinase (Raf-1), mitogen-activated protein kinase kinase (MAPKK), MAP kinases (MAPKs) and 90-kDa ribosomal S6 kinase (p90^rsk) in neonatal rat cardiomyocytes. Mechanical stretch rapidly activated Raf-1 and its maximal activation was observed at 1–2 min after stretch. The activity of MAPKK was also increased by stretch, with a peak at 5 min after stretch. In addition, MAPKs and p90^rsk were maximally activated at 8 min and at 10–30 min after stretch, respectively. Next, the relationship between mechanical stress-induced hypertrophy and the cardiac renin-angiotensin system was investigated. When the stretch-conditioned culture medium was transferred to the culture dish of non-stretched cardiac myocytes, the medium activated MAPK activity slightly but significantly, and the activation was completely blocked by the type 1 angiotensin II receptor antagonist, CV-11974. However, activation of Raf-1 and MAPKs provoked by stretching cardiomyocytes was only partially suppressed by pretreatment with CV-11974. These results suggest that mechanical stress activates the protein kinase cascade of phosphorylation in cardiac myocytes in the order of Raf-1, MAPKK, MAPKs and p90^rsk, and that angiotensin II, which is secreted from stretched myocytes, activates a part of these protein kinases.Abbreviations MAPK mitogen-activated protein kinase - MAPKK MAP kinase kinase - Raf-1 - Raf- 1 kinase p90^rsk, 90 kDa ribosomal S6 kinase; AngII - angiotensin II - MAPKKK MAP kinase kinase kinase - rMAPK recombinant MAPKK fused to gluthathione S transferase - MMAKK recombinant MAPK fused to maltose binding protein - MBP myelin basic protein - ACE angiotensin-converting enzyme     

An angular velocity profile in cycling derived from mechanical energy analysis

The contributions of this article are twofold. One is procedure for determining the angular velocity profile in seated cycling that maintains the total mechanical energy of both legs constant. A five-bar linkage model (thigh, shank, foot, crank and frame) of seated (fixed hip) cycling served for the derivation of the equations to compute potential and kinetic energies of the leg segments over a complete crank cycle. With experimentally collected pedal angle data as input, these equations were used to compute the total combined mechanical energy (sum of potential and kinetic energies of the segments of both legs) for constant angular velocity pedalling at 90 rpm. Total energy varied indicating the presence of internal work. Motivated by a desire to test the hypothesis that reducing internal work in cycling will reduce energy expenditure, a procedure was developed for determining the angular velocity profile that eliminated any change in total energy. Using data recorded from five subjects, this procedure was used to determine a reference profile for an average equivalent cadence of 90 rpm. The phase of this profile is such that highest and lowest angular velocities occur when the cranks are near vertical and horizontal respectively. The second contribution is the testing of the hypothesis that the reference angular velocity profile serves to effectively reduce internal work for the subjects whose data were used to develop this profile over the range of pedalling rates (80-100 rpm) naturally preferred. In this range, the internal work was decreased a minimum of 48% relative to the internal work associated with constant angular velocity pedalling. The acceptance of this hypothesis has relevance to the protocol for future experiments which explore the effect of reduced internal work on energy expenditure in cycling.     

An integrated proteomics analysis of bone tissues in response to mechanical stimulation

Bone cells can sense physical forces and convert mechanical stimulation conditions into biochemical signals that lead to expression of mechanically sensitive genes and proteins. However, it is still poorly understood how genes and proteins in bone cells are orchestrated to respond to mechanical stimulations. In this research, we applied integrated proteomics, statistical, and network biology techniques to study proteome-level changes to bone tissue cells in response to two different conditions, normal loading and fatigue loading. We harvested ulna midshafts and isolated proteins from the control, loaded, and fatigue loaded Rats. Using a label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) experimental proteomics technique, we derived a comprehensive list of 1,058 proteins that are differentially expressed among normal loading, fatigue loading, and controls. By carefully developing protein selection filters and statistical models, we were able to identify 42 proteins representing 21 Rat genes that were significantly associated with bone cells' response to quantitative changes between normal loading and fatigue loading conditions. We further applied network biology techniques by building a fatigue loading activated protein-protein interaction subnetwork involving 9 of the human-homolog counterpart of the 21 rat genes in a large connected network component. Our study shows that the combination of decreased anti-apoptotic factor, Raf1, and increased pro-apoptotic factor, PDCD8, results in significant increase in the number of apoptotic osteocytes following fatigue loading. We believe controlling osteoblast differentiation/proliferation and osteocyte apoptosis could be promising directions for developing future therapeutic solutions for related bone diseases.     

Effects of mechanical assistance on muscle activity and motor performance during isometric elbow flexion

Mechanical assistance on joint movement is generally beneficial; however, its effects on cooperative performance and muscle activity needs to be further explored. This study examined how motor performance and muscle activity are altered when mechanical assistance is provided during isometric force control of ramp-down and hold phases. Thirteen right-handed participants (age: 24.7 ± 1.8 years) performed trajectory tracking tasks. Participants were asked to maintain the reference magnitude of 47 N (REF) during isometric elbow flexion. The force was released to a step-down magnitude of either 75% REF or 50% REF and maintained, with and without mechanical assistance. The ramp-down durations of force release were set to 0.5, 2.5, or 5.0 s. Throughout the experiment, we measured the following: (1) the force output using load cells to compute force variability and overshoot ratio; (2) peak perturbation on the elbow movement using an accelerometer; (3) the surface electromyography (sEMG) from biceps brachii and triceps brachii muscles; and (4) EMG oscillation from the biceps brachii muscle in the bandwidth of 15–45 Hz. Our results indicated that mechanical assistance, which involved greater peak perturbation, demonstrated lower force variability than non-assistance (p < 0.01), while EMG oscillation in the biceps brachii muscle from 15 to 45 Hz was increased (p < 0.05). These findings imply that if assistive force is provided during isometric force control, the central nervous system actively tries to stabilize motor performance by controlling specific motor unit activity in the agonist muscle.     

心肌细胞的机械感受机制

心肌细胞的机械感受机制是心肌生物力学研究的重要内容之一。新近研究表明,其机制主要包括四个方面：⑴细胞膜直接感受;⑵细胞间质－细胞骨架拉动传递;⑶自分泌与旁分泌生长因子与前列腺素等;⑷氧自由基介导。     

Rheological responses of cardiac fibroblasts to mechanical stretch

Rheological characterization of cells using passive particle tracking techniques can yield substantial information regarding local cellular material properties. However, limited work has been done to establish the changes in material properties of mechanically-responsive cells that experience external stimuli. In this study, cardiac fibroblasts plated on either fibronectin or collagen were treated with cytochalasin, mechanically stretched, or both, and their trajectories and complex moduli were extracted. Results demonstrate that both solid and fluid components were altered by such treatments in a receptor-dependent manner, and that, interestingly, cells treated with cytochalasin were still capable of stiffening in response to mechanical stimuli despite gross stress fiber disruption. These results suggest that the material properties of cells are dependent on a variety of environmental cues and can provide insight into physiological and disease processes.     

Aligned human cardiac syncytium for in vitro analysis of electrical,structural, and mechanical readouts

Human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) have emerged as an exciting new tool for cardiac research and can serve as a preclinical platform for drug development and disease modeling studies. However, these aspirations are limited by current culture methods in which hPSC‐CMs resemble fetal human cardiomyocytes in terms of structure and function. Herein we provide a novel in vitro platform that includes patterned extracellular matrix with physiological substrate stiffness and is amenable to both mechanical and electrical analysis. Micropatterned lanes promote the cellular and myofibril alignment of hPSC‐CMs while the addition of micropatterned bridges enable formation of a functional cardiac syncytium that beats synchronously over a large two‐dimensional area. We investigated the electrophysiological properties of the patterned cardiac constructs and showed they have anisotropic electrical impulse propagation, as occurs in the native myocardium, with speeds 2x faster in the primary direction of the pattern as compared to the transverse direction. Lastly, we interrogated the mechanical function of the pattern constructs and demonstrated the utility of this platform in recording the strength of cardiomyocyte contractions. This biomimetic platform with electrical and mechanical readout capabilities will enable the study of cardiac disease and the influence of pharmaceuticals and toxins on cardiomyocyte function. The platform also holds potential for high throughput evaluation of drug safety and efficacy, thus furthering our understanding of cardiovascular disease and increasing the translational use of hPSC‐CMs.     

An epigenome-wide association analysis of cardiac autonomic responses among a population of welders

DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population.     

Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function

Increased heart size is a major risk factor for heart failure and premature mortality. Although abnormal heart growth subsequent to hypertension often accompanies disturbances in mechano-energetics and cardiac efficiency, it remains uncertain whether hypertrophy is their primary driver. In this study, we aimed to investigate the direct association between cardiac hypertrophy and cardiac mechano-energetics using isolated left-ventricular trabeculae from a rat model of primary cardiac hypertrophy and its control. We evaluated energy expenditure (heat output) and mechanical performance (force length work production) simultaneously at a range of preloads and afterloads in a microcalorimeter, we determined energy expenditure related to cross-bridge cycling and Ca²⁺ cycling (activation heat), and we quantified energy efficiency. Rats with cardiac hypertrophy exhibited increased cardiomyocyte length and width. Their trabeculae showed mechanical impairment, evidenced by lower force production, extent and kinetics of shortening, and work output. Lower force was associated with lower energy expenditure related to Ca²⁺ cycling and to cross-bridge cycling. However, despite these changes, both mechanical and cross-bridge energy efficiency were unchanged. Our results show that cardiac hypertrophy is associated with impaired contractile performance and with preservation of energy efficiency. These findings provide direction for future investigations targeting metabolic and Ca²⁺ disturbances underlying cardiac mechanical and energetic impairment in primary cardiac hypertrophy.     

An analysis of calcium effects on diastolic depolarization in sheep cardiac Purkinje fibers

The events by which [Ca]O modifies diastolic depolarization (DD) were analyzed in sheep cardiac Purkinje fibers perfused in vitro. Cs (2 mM) reduced diastolic depolarization (DD) at different [Ca]O and in 10.8 mM [Ca]O revealed an oscillatory potential (VOS) and the decay of a prolonged depolarization (Vex). In the presence of Cs, procedures that reduce Cai (a slower driving rate, lower [Ca]O or tetrodotoxin) abolished VOS and Vex and partially restored DD. In 10.8 mM [Ca]O and at all driving rates, Cs reduced DD slope, DD amplitude and VOS amplitude but had little effect on the VOS time to peak. In 10.8 mM [Ca]O, decreasing calcium overload by different means (2.6 microM TTX, 0.2 mM Cd) abolished VOS and decreased DD slope and amplitude. Substituting Na with Li induced marked aftercontractions but small VOS. In 10.8 mM [Ca]O, Li increased the amplitude of the aftercontractions and decreased that of VOS. Li also depolarized slightly the resting membrane and abolished the voltage undershoot (Emax) at the end of the action potential. In low [K]O, Li repolarized the resting membrane but the repolarization was maintained only in the presence of Ca. It is concluded that Ca overload causes both VOS and Vex which can either be masked by or can mask DD depending on the magnitude of DD and of Ca overload. VOS is apparently caused by an electrogenic Na-Ca exchange since Li-induced Ca overload increases the aftercontraction but decreases VOS.     

机械措施控制加拿大萨斯克彻温草场丛生卷柏生长的经济分析

对加拿大萨斯克彻温省干旱棕色土壤带、湿润棕色土壤带及黑棕色土壤带上的沙土和壤土草场区所应用的挖鱼鳞坑和犁翻两种机械措施控制丛生卷柏侵蚀天然草场的效果进行了经济效益分析。分析结果表明 :当市场折扣率为 8%和 10 %时 ,犁翻处理在任何草场区实施均在 2 0 a内不能收回投入 ,说明该处理在经济上是不可行的 ;而挖鱼鳞坑在黑棕色土壤带实施分别需要10 a和 11a才能收回投入 ,在湿润棕色土壤带分别需 12 a和 14 a,而在干燥棕色土壤带则分别需 15 a和 2 2 a。但在实际中 ,这两种处理是否能发挥 2 0 a以上的经济效益还需进一步研究。草场管理者应根据两种处理控制丛生卷柏效果及饲草产量的增量来确定净现值和内部报酬率 ,估测收回投入的年限 ,最终作出合理的经济决策。当然 ,如果考虑到铲除丛生卷柏所带来的一些生态方面的争议 ,草场管理者应慎重考虑其他一些改良措施 ,如改进放牧管理 ,施化肥及播种目标草种等 ,以达到取得经济效益的目的     

An analysis of turbulent shear stresses in leakage flow through a bileaflet mechanical prostheses

In this work, estimates of turbulence were made from pulsatile flow laser Doppler velocimetry measurements using traditional phase averaging and averaging after the removal of cyclic variation. These estimates were compared with estimates obtained from steady leakage flow LDV measurements and an analytical method. The results of these studies indicate that leakage jets which are free and planar in shape may be more unstable than other leakage jets, and that cyclic variation does not cause a gross overestimation of the Reynolds stresses at large distances from the leakage jet orifice.     

Current strategies of mechanical stimulation for maturation of cardiac microtissues

The most advanced in vitro cardiac models are today based on the use of induced pluripotent stem cells (iPSCs); however, the maturation of cardiomyocytes (CMs) has not yet been fully achieved. Therefore, there is a rising need to move towards models capable of promoting an adult-like cardiomyocytes phenotype. Many strategies have been applied such as co-culture of cardiomyocytes, with fibroblasts and endothelial cells, or conditioning them through biochemical factors and physical stimulations. Here, we focus on mechanical stimulation as it aims to mimic the different mechanical forces that heart receives during its development and the post-natal period. We describe the current strategies and the mechanical properties necessary to promote a positive response in cardiac tissues from different cell sources, distinguishing between passive stimulation, which includes stiffness, topography and static stress and active stimulation, encompassing cyclic strain, compression or perfusion. We also highlight how mechanical stimulation is applied in disease modelling.