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Biomedical subjects

Toshiaki Hisada

Publications and source records attributed to Toshiaki Hisada.

6 recordsLinked to original sources

Finite element contact analysis of the hip joint.

The hip joint plays an important role in the musculoskeletal system; however, current knowledge of the mechanics of the hip joint, especially with regard to the distribution of stress, remains limited. In experimental research, difficulties arise during reproduction of physiological conditions of daily activities and practicable measurement of locations inside the hip joint without violating the physiological environment. On the other hand, numerical approaches, such as finite element analysis, have become useful tools in the field of biomechanics. In finite element contact analysis of the hip joint, due to discretization of contact surfaces, computational instability might occur when the contact nodes move near the edges of the contact elements. In this study, to overcome this problem, a contact smoothing approach was introduced by applying Gregory patches. Contact analysis of the hip joint was then performed for three representative daily activities; i.e., walking, rising up from a chair and knee bending. The effectiveness of the adopted smoothing approach was verified by comparing the results with those obtained experimentally. The distribution and history of contact stress, which have heretofore been scarcely reported, were also obtained and the implications associated with osteoarthritis were discussed.

Algorithms↗

Microtubules modulate the stiffness of cardiomyocytes against shear stress.

Although microtubules are involved in various pathological conditions of the heart including hypertrophy and congestive heart failure, the mechanical role of microtubules in cardiomyocytes under such conditions is not well understood. In the present study, we measured multiple aspects of the mechanical properties of single cardiomyocytes, including tensile stiffness, transverse (indentation) stiffness, and shear stiffness in both transverse and longitudinal planes using carbon fiber-based systems and compared these parameters under control, microtubule depolymerized (colchicine treated), and microtubule hyperpolymerized (paclitaxel treated) conditions. From all of these measurements, we found that only the stiffness against shear in the longitudinal plane was modulated by the microtubule cytoskeleton. A simulation model of the myocyte in which microtubules serve as compression-resistant elements successfully reproduced the experimental results. In the complex strain field that living myocytes experience in the body, observed changes in shear stiffness may have a significant influence on the diastolic property of the diseased heart.

Animals↗

Three-dimensional simulation of calcium waves and contraction in cardiomyocytes using the finite element method.

To investigate the characteristics and underlying mechanisms of Ca(2+) wave propagation, we developed a three-dimensional (3-D) simulator of cardiac myocytes, in which the sarcolemma, myofibril, and Z-line structure with Ca(2+) release sites were modeled as separate structures using the finite element method. Similarly to previous studies, we assumed that Ca(2+) diffusion from one release site to another and Ca(2+)-induced Ca(2+) release were the basic mechanisms, but use of the finite element method enabled us to simulate not only the wave propagation in 3-D space but also the active shortening of the myocytes. Therefore, in addition to the dependence of the Ca(2+) wave propagation velocity on the sarcoplasmic reticulum Ca(2+) content and affinity of troponin C for Ca(2+), we were able to evaluate the influence of active shortening on the propagation velocity. Furthermore, if the initial Ca(2+) release took place in the proximity of the nucleus, spiral Ca(2+) waves evolved and spread in a complex manner, suggesting that this phenomenon has the potential for arrhythmogenicity. The present 3-D simulator, with its ability to study the interaction between Ca(2+) waves and contraction, will serve as a useful tool for studying the mechanism of this complex phenomenon.

Animals↗

Effect on endothelial cell gene expression of shear stress, oxygen concentration, and low-density lipoprotein as studied by a novel flow cell culture system.

A new cell culture system has been developed that reflects the vascular microenvironment. By means of this system the cultured cells are exposed not only to shear stress by the circulating culture medium, but also to an oxygen concentration gradient and certain critical blood components such as low-density lipoprotein (LDL) and monocytes. DNA microarray analysis was performed for human umbilical vein endothelial cells cultured in this system in the absence and presence of laminar flow at a low shear stress, 0.2 dyn/cm(2). In addition to shear stress, either an oxygen concentration gradient, or LDL (1 mg/ml), or both were applied. Many Nrf-2-regulating genes, such as heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, solute carrier family 7 No. 11, and glutamate-cysteine ligase modifier subunit, were induced by laminar flow at very low shear stress regardless of the additional conditions. Certain genes were specifically affected by exposure to the oxygen gradient and/or LDL under shear stress, but the degree was very low. These results suggest that shear stress is the most critical factor affecting gene expression in endothelial cells and that Nrf-2-regulating proteins may contribute to protecting endothelial cells against other vascular stress. This system should provide highly relevant and useful information about both vascular physiology and pathology, in the latter on such urgent matters as the specific steps involved in atherogenesis.

Base Sequence↗

Single cell mechanics of rat cardiomyocytes under isometric, unloaded, and physiologically loaded conditions.

One of the most salient characteristics of the heart is its ability to adjust work output to external load. To examine whether a single cardiomyocyte preparation retains this property, we measured the contractile function of a single rat cardiomyocyte under a wide range of loading conditions using a force-length measurement system implemented with adaptive control. A pair of carbon fibers was used to clamp the cardiomyocyte, attached to each end under a microscope. One fiber was stiff, serving as a mechanical anchor, while the bending motion of the compliant fiber was monitored for force-length measurement. Furthermore, by controlling the position of the compliant fiber using a piezoelectric translator based on adaptive control, we could change load dynamically during contractions. Under unloaded conditions, maximal shortening velocity was 106 +/- 8.9 microm/s (n = 13 cells), and, under isometric conditions, peak developed force reached 5,720 nN (41.6 +/- 5.6 mN/mm(2); n = 17 cells). When we simulated physiological working conditions consisting of an isometric contraction, followed by shortening and relaxation, the average work output was 828 +/- 123 J/m(3) (n = 20 cells). The top left corners of tension-length loops obtained under all of these conditions approximate a line, analogous to the end-systolic pressure-volume relation of the ventricle. All of the functional characteristics described were analogous to those established by studies using papillary muscle or trabeculae preparations. In conclusion, the present results confirmed the fact that each myocyte forms the functional basis for ventricular function and that single cell mechanics can be a link between subcellular events and ventricular mechanics.

Animals↗

Multiphysics simulation of left ventricular filling dynamics using fluid-structure interaction finite element method.

To relate the subcellular molecular events to organ level physiology in heart, we have developed a three-dimensional finite-element-based simulation program incorporating the cellular mechanisms of excitation-contraction coupling and its propagation, and simulated the fluid-structure interaction involved in the contraction and relaxation of the human left ventricle. The FitzHugh-Nagumo model and four-state model representing the cross-bridge kinetics were adopted for cellular model. Both ventricular wall and blood in the cavity were modeled by finite element mesh. An arbitrary Lagrangian Eulerian finite element method with automatic mesh updating has been formulated for large domain changes, and a strong coupling strategy has been taken. Using electrical analog of pulmonary circulation and left atrium as a preload and the windkessel model as an afterload, dynamics of ventricular filling as well as ejection was simulated. We successfully reproduced the biphasic filling flow consisting of early rapid filling and atrial contraction similar to that reported in clinical observation. Furthermore, fluid-structure analysis enabled us to analyze the wave propagation velocity of filling flow. This simulator can be a powerful tool for establishing a link between molecular abnormality and the clinical disorder at the macroscopic level.

Biophysical Phenomena↗