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Article ; Online: Low-energy defibrillation using a base-apex epicardial electrode.

Okada, Jun-Ichi / Washio, Takumi / Sugiura, Seiryo / Hisada, Toshiaki

Pacing and clinical electrophysiology : PACE

2023 Volume 46, Issue 11, Page(s) 1325–1332

Abstract: Background: Current implantable cardioverter defibrillators (ICDs) require electric conduction with high voltage and high energy, which can impair cardiac function and induce another malignant arrhythmia. As a result, there has been a demand for an ICD ... ...

Abstract	Background: Current implantable cardioverter defibrillators (ICDs) require electric conduction with high voltage and high energy, which can impair cardiac function and induce another malignant arrhythmia. As a result, there has been a demand for an ICD that can effectively operate with lower energy to mitigate the risks of a strong electric shock. Methods: A pair of sheet-shaped electrodes covering the heart were analyzed in three configurations (top-bottom, left-right, and front-back) using a heart simulator. We also varied the distance between the two electrodes (clearance) to identify the electrode shape with the lowest defibrillation threshold (DFT). We also investigated the ICD shock waveform, shock direction, and the effect of the backside insulator of the electrode. Results: The DFT was high when the clearance was too small and the DFT was high even when the clearance was too large, suggesting that an optimal value clearance. The top-bottom electrodes with optimal clearance showed the lowest DFT when the biphasic shocks set the top electrode to a high potential first and then the bottom electrode was set to a high potential. An interval between a first shock waveform and a second shock waveform should be provided for low-energy defibrillation. Because the insulator prevents unnecessary current flow to the backside, the DFT of the electrodes with insulators is less than those without insulators. Conclusion: Painless defibrillation using sheet-shaped electrodes on the epicardium is predicated on the basis of results using a heart simulator.
MeSH term(s)	Humans ; Electric Countershock/methods ; Defibrillators, Implantable ; Ventricular Fibrillation ; Pericardium
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	424437-0
ISSN	1540-8159 ; 0147-8389
ISSN (online)	1540-8159
ISSN	0147-8389
DOI	10.1111/pace.14832
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Article ; Online: Transition mechanisms from atrial flutter to atrial fibrillation during anti-tachycardia pacing therapy.

Okada, Jun-Ichi / Washio, Takumi / Sugiura, Seiryo / Hisada, Toshiaki

Pacing and clinical electrophysiology : PACE

2023 Volume 46, Issue 12, Page(s) 1509–1518

Abstract: Background: Atrial anti-tachycardia pacing (aATP) has been shown to be effective for the termination of atrial tachyarrhythmias, but its success rate is still not high enough.: Objective: The main objective of this study was to investigate the ... ...

Abstract	Background: Atrial anti-tachycardia pacing (aATP) has been shown to be effective for the termination of atrial tachyarrhythmias, but its success rate is still not high enough. Objective: The main objective of this study was to investigate the mechanisms of atrial flutter (AFL) termination by aATP and the transition from AFL to atrial fibrillation (AF) during aATP. Methods: We developed a multi-scale model of the human atrium based on magnetic resonance images and examined the atrial electrophysiology of AFL during aATP with a ramp protocol. Results: In successful cases of aATP, paced excitation entered the excitable gap and collided with the leading edge of the reentrant wave front. Furthermore, the excitation propagating in the opposite direction collided with the trailing edge of the reentrant wave to terminate AFL. The second collision was made possible by the distribution of the wave propagation velocity in the atria. The detailed analysis revealed that the slowing of propagation velocity occurred at the exit of the sub-Eustachian isthmus, probably due to source-sink mismatch. During the transition from AFL to AF, the excitation collided with the refractory zone of the preceding wave and broke into multiple wave fronts to induce AF. A similar observation was made for the transition from AF to sinus rhythm. In both cases, the complex anatomy of the atria played an essential role. Conclusion: The complex anatomy of atria plays an essential role in the maintenance of stable AFL and its termination by aATP, which were revealed by the realistic three-dimensional simulation model.
MeSH term(s)	Humans ; Atrial Flutter/therapy ; Atrial Fibrillation/therapy ; Cardiac Pacing, Artificial ; Tachycardia/therapy ; Heart Atria
Language	English
Publishing date	2023-11-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424437-0
ISSN	1540-8159 ; 0147-8389
ISSN (online)	1540-8159
ISSN	0147-8389
DOI	10.1111/pace.14863
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Article ; Online: UT-Heart: A Finite Element Model Designed for the Multiscale and Multiphysics Integration of our Knowledge on the Human Heart.

Sugiura, Seiryo / Okada, Jun-Ichi / Washio, Takumi / Hisada, Toshiaki

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2399, Page(s) 221–245

Abstract: To fully understand the health and pathology of the heart, it is necessary to integrate knowledge accumulated at molecular, cellular, tissue, and organ levels. However, it is difficult to comprehend the complex interactions occurring among the building ... ...

Abstract	To fully understand the health and pathology of the heart, it is necessary to integrate knowledge accumulated at molecular, cellular, tissue, and organ levels. However, it is difficult to comprehend the complex interactions occurring among the building blocks of biological systems across these scales. Recent advances in computational science supported by innovative high-performance computer hardware make it possible to develop a multiscale multiphysics model simulating the heart, in which the behavior of each cell model is controlled by molecular mechanisms and the cell models themselves are arranged to reproduce elaborate tissue structures. Such a simulator could be used as a tool not only in basic science but also in clinical settings. Here, we describe a multiscale multiphysics heart simulator, UT-Heart, which uses unique technologies to realize the abovementioned features. As examples of its applications, models for cardiac resynchronization therapy and surgery for congenital heart disease will be also shown.
MeSH term(s)	Computer Simulation ; Finite Element Analysis ; Heart ; Humans
Language	English
Publishing date	2022-05-23
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1831-8_10
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Article ; Online: Fish Bone Protruding From Stool in a Colonic Diverticulum.

Hamada, Kenta / Kubota, Jun-Ichi / Okada, Hiroyuki

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2020 Volume 19, Issue 9, Page(s) A23–A24

MeSH term(s)	Animals ; Diverticulum, Colon ; Feces ; Humans ; Tomography, X-Ray Computed
Language	English
Publishing date	2020-05-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2020.05.040
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Zs.A 5836: Show issues

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Article ; Online: Cross-Correlation of Confocal Images for Excised Breast Tissues of Total Mastectomy.

Song, Hang / Sasada, Shinsuke / Kadoya, Takayuki / Arihiro, Koji / Okada, Morihito / Xiao, Xia / Ishikawa, Tomomi / O'Loughlin, Declan / Takada, Jun-Ichi / Kikkawa, Takamaro

IEEE transactions on bio-medical engineering

2024 Volume 71, Issue 5, Page(s) 1705–1716

Abstract: Object: The purpose of this study is to develop an image artifact removal method for radar-based microwave breast imaging and demonstrates the detectability on excised breast tissues of total mastectomy.: Methods: A cross-correlation method was ... ...

Abstract	Object: The purpose of this study is to develop an image artifact removal method for radar-based microwave breast imaging and demonstrates the detectability on excised breast tissues of total mastectomy. Methods: A cross-correlation method was proposed and measurements were conducted. A hand-held radar-based breast cancer detector was utilized to measure a breast at different orientations. Images were generated by multiplying the confocal image data from two scans after cross-correlation. The optimum reconstruction permittivity values were extracted by the local maxima of the confocal image intensity as a function of reconstruction permittivity. Results: With the proposed cross-correlation method, the contrast of the imaging result was enhanced and the clutters were removed. The proposed method was applied to 50 cases of excised breast tissues and the detection sensitivity of 72% was achieved. With the limited number of samples, the dependency of detection sensitivity on the breast size, breast density, and tumor size were examined. Conclusion and significance: The detection sensitivity was strongly influenced by the breast density. The sensitivity was high for fatty breasts, whereas the sensitivity was low for heterogeneously dense breasts. In addition, it was observed that the sensitivity was high for extremely dense breast. This is the first detailed report on the excised breast tissues.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/surgery ; Mastectomy/methods ; Breast/diagnostic imaging ; Breast/surgery ; Microwave Imaging ; Microscopy, Confocal/methods ; Middle Aged ; Sensitivity and Specificity ; Adult ; Artifacts ; Algorithms ; Aged
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	160429-6
ISSN	1558-2531 ; 0018-9294
ISSN (online)	1558-2531
ISSN	0018-9294
DOI	10.1109/TBME.2023.3348480
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Zs.A 425: Show issues

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Article: A thermodynamically consistent monte carlo cross-bridge model with a trapping mechanism reveals the role of stretch activation in heart pumping.

Yoneda, Kazunori / Kanada, Ryo / Okada, Jun-Ichi / Watanabe, Masahiro / Sugiura, Seiryo / Hisada, Toshiaki / Washio, Takumi

Frontiers in physiology

2022 Volume 13, Page(s) 855303

Abstract: Changes in intracellular calcium concentrations regulate heart beats. However, the decline in the left ventricular pressure during early diastole is much sharper than that of the ... ...

Abstract	Changes in intracellular calcium concentrations regulate heart beats. However, the decline in the left ventricular pressure during early diastole is much sharper than that of the Ca
Language	English
Publishing date	2022-09-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.855303
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Article ; Online: Reliable detection of genetic alterations in cyst fluid DNA for the diagnosis of brain tumors.

Journal of neuro-oncology

2024 Volume 166, Issue 2, Page(s) 273–282

Abstract: Purpose: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) ... ...

Abstract	Purpose: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. Methods: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. Results: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. Conclusion: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.
MeSH term(s)	Humans ; Oligodendroglioma/diagnosis ; Oligodendroglioma/genetics ; Oligodendroglioma/pathology ; Cyst Fluid ; Brain Neoplasms/diagnosis ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Mutation ; Cell-Free Nucleic Acids ; Multiplex Polymerase Chain Reaction ; DNA
Chemical Substances	Cell-Free Nucleic Acids ; DNA (9007-49-2)
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	604875-4
ISSN	1573-7373 ; 0167-594X
ISSN (online)	1573-7373
ISSN	0167-594X
DOI	10.1007/s11060-023-04555-5
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Zs.A 1825: Show issues

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Article: Using Systolic Local Mechanical Load to Predict Fiber Orientation in Ventricles.

Washio, Takumi / Sugiura, Seiryo / Okada, Jun-Ichi / Hisada, Toshiaki

Frontiers in physiology

2020 Volume 11, Page(s) 467

Abstract: A simple rule adopted for myofiber reorientation in the ventricles is pursued by taking the microscopic branching network of myocytes into account. The macroscopic active tension generated on the microscopic branching structure is modeled by a ... ...

Abstract	A simple rule adopted for myofiber reorientation in the ventricles is pursued by taking the microscopic branching network of myocytes into account. The macroscopic active tension generated on the microscopic branching structure is modeled by a multidirectional active stress tensor, which is defined as a function of the strains in the branching directions. In our reorientation algorithm, the principal direction of the branching network is updated so that it turns in the direction of greater active tension in the isovolumetric systole. Updates are performed step-by-step after the mechanical equilibrium has been attained with the current fiber structure. Starting from a nearly flat distribution of the principal fiber orientation along the circumferential direction, the reoriented fiber helix angles range from 70 to 40° at epicardium and from 60 to 80° at endocardium, in agreement with experimental observations. The helical ventricular myocardial band of Torrent-Guasp's model and the apical spiral structure of Rushmer's model are also reconstructed by our algorithm. Applying our algorithm to the infarcted ventricle model, the fiber structure near the infarcted site is remodeled so that the helix angle becomes steeper with respect to the circumferential direction near the epicardial surface. Based on our numerical analysis, we draw the following conclusions. (i) The multidirectional active tension based on the microscopic branching network is potentially used to seek tighter connection with neighboring aggregates. (ii) The thickening and thinning transitions in response to active tension in each myocyte allow the macroscopic principal fiber orientation of the microscopic branching network to move toward the direction of greater active tension. (iii) The force-velocity relationship is the key factor in transferring the fiber shortening strain to the magnitude of active tensions used in the myofiber reorientation. (iv) The algorithm naturally leads to homogeneity in the macroscopic active tension and the fiber shortening strain, and results in near-optimal pumping performance. (v) However, the reorientation mechanism may degrade the pumping performance if there is severely inhomogeneous contractility resulting from infarction. Our goal is to provide a tool to predict the fiber architecture of various heart disease patients for numerical simulations of their treatment plans.
Language	English
Publishing date	2020-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2020.00467
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Article ; Online: Tuberculosis osteomyelitis in an old fused hip; activated by prednisolone, salazosulfapyridine, and low-dose methotrexate therapy in a patient with rheumatoid arthritis.

Okada, Fumi / Fukushi, Jun-Ichi / Matsubara, Hirokazu / Ishitani, Ei-Ichi / Sonoda, Yasuo / Katsuki, Ichiro

Modern rheumatology case reports

2020 Volume 4, Issue 2, Page(s) 171–175

Abstract: Osteoarticular tuberculosis can occur in patients with rheumatoid arthritis (RA) receiving immunosuppressive therapy. Here, we describe a case of tubercular osteomyelitis in an old fused hip of a patient with RA who received prednisolone, ... ...

Abstract	Osteoarticular tuberculosis can occur in patients with rheumatoid arthritis (RA) receiving immunosuppressive therapy. Here, we describe a case of tubercular osteomyelitis in an old fused hip of a patient with RA who received prednisolone, salazosulfapyridine (SASP), and low-dose methotrexate (MTX). A 77-year-old man with a 4-year history of RA was admitted with a complaint of general fatigue. His symptoms of RA had been well controlled with a combination of prednisolone, SASP, and low-dose MTX. Because the laboratory data showed an increase in serum C-reactive protein levels, we suspected pneumonia. There was expansion of a pre-existing consolidation in the right lower lobe of his lung on chest computed tomography, and the sputum culture was positive for
MeSH term(s)	Aged ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/therapeutic use ; Antitubercular Agents/therapeutic use ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/drug therapy ; Drug Therapy, Combination ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/therapeutic use ; Male ; Methotrexate/administration & dosage ; Osteomyelitis/diagnosis ; Osteomyelitis/drug therapy ; Osteomyelitis/etiology ; Prednisolone/administration & dosage ; Sulfasalazine/administration & dosage ; Treatment Outcome ; Tuberculosis, Osteoarticular/diagnosis ; Tuberculosis, Osteoarticular/drug therapy ; Tuberculosis, Osteoarticular/etiology
Chemical Substances	Antirheumatic Agents ; Antitubercular Agents ; Immunosuppressive Agents ; Sulfasalazine (3XC8GUZ6CB) ; Prednisolone (9PHQ9Y1OLM) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2020-03-13
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	2472-5625
ISSN (online)	2472-5625
DOI	10.1080/24725625.2020.1739194
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Article ; Online: Chloroquine and hydroxychloroquine provoke arrhythmias at concentrations higher than those clinically used to treat COVID‐19

Jun‐ichi Okada / Takashi Yoshinaga / Takumi Washio / Kohei Sawada / Seiryo Sugiura / Toshiaki Hisada

Clinical and Translational Science, Vol 14, Iss 3, Pp 1092-

A simulation study

2021 Volume 1100

Abstract: Abstract The risk of fatal arrhythmias is the major concern for using chloroquine (CQ) or hydroxychloroquine (HCQ) to treat coronavirus disease 2019 (COVID‐19), but the reported number of life‐threatening arrhythmic events or deaths is relatively small. ... ...

Abstract	Abstract The risk of fatal arrhythmias is the major concern for using chloroquine (CQ) or hydroxychloroquine (HCQ) to treat coronavirus disease 2019 (COVID‐19), but the reported number of life‐threatening arrhythmic events or deaths is relatively small. The objective of this study was to assess the arrhythmogenic risk of these two drugs using a multiscale heart simulation, which allows testing even at high concentrations, including those that cause fatal arrhythmias. We measured the inhibitory action of CQ, HCQ, and HCQ with 30 μM azithromycin (AZ) on six ion currents (fast [INa] and late [INa,L] components of the sodium current, L‐type calcium current [ICa,L], rapid [IKr/hERG], and slow [IKs] components of delayed rectifier potassium, and inward rectifier potassium [IK1]) over a wide range of concentrations using the automated patch‐clamp system. Using the concentration–inhibition relationship that was thus obtained, we simulated the drug effects while increasing the concentration until the life‐threatening arrhythmia, torsade de pointes (TdP), was observed. The obtained threshold concentrations for TdP were 12.5, 35, and 22.5 μM for CQ, HCQ, and HCQ with AZ, respectively. Adding therapeutic concentrations of mexiletine or verapamil successfully prevented the occurrence of TdP, and verapamil was more effective. CQ, HCQ, and HCQ with AZ thresholds for TdP were larger than both antiviral concentrations that were reported by in vitro experiments and free plasma concentrations that were attained by the clinically used dosage. The current simulation data provided a safety margin to the currently used clinical dose for CQ and HCQ/AZ. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Despite the potent in vitro antiviral effect, clinical trials have failed to show the therapeutic effects of chloroquine (CQ) and hydroxychloroquine (HCQ)/azithromycin (AZ) to treat coronavirus disease 2019. Torsadogenic potentials may limit the dosage of these drugs, but the reported incidence of fatal arrhythmias is rare. ...
Keywords	Therapeutics. Pharmacology ; RM1-950 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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