| Project/Area Number |
20K12046
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 62010:Life, health and medical informatics-related
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| Research Institution | The University of Aizu |
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Principal Investigator |
Maxim・V Ryzhii 会津大学, コンピュータ理工学部, 上級准教授 (50254082)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | atrioventricular node / rabbit heart model / Aliev-Panfilov model / dual pathway / cardiac conduction curve / coupling asymmetry / retrograde conduction / ladder diagram / Corrado-Niederer / Aliev-Panfilov / "natural pacemaker" / "nonlinear equation" / "dual pathway" / "cardiac model" / intestine / "sinoatrial node" / Mitchell-Schaeffer / pacemaker / nonlinear equation / oscillator / cardiac model / arrhythmia / computer modeling / conduction system / implantable device |
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| Outline of Research at the Start |
We are going to develop a simple comprehensive computer model of conduction system of the heart for implantable pacemaker testing and cardiac arrhythmia study. Using the developed model, we will perform various computer simulations of the cardiac rhythm disturbances, and investigate possible methods of their control.
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| Outline of Annual Research Achievements |
The atrioventricular node (AVN) is considered a ”black box”, and the functioning of its dual pathways remains controversial and not fully understood. We have developed a compact, computationally lightweight multi-functional rabbit AVN model based on the Aliev-Panfilov two-variable cardiac cell model. The 1D AVN model includes fast and slow pathways, primary pacemaking in the sinoatrial node, and subsidiary pacemaking in the slow pathway.
We implemented the asymmetry of coupling between model cells to obtain the direction-dependent conduction properties of the AVN, together with gradients of intercellular coupling and cell refractoriness. The AVN model demonstrates broad functionality, including normal sinus rhythm, AVN automaticity, filtering of high-rate atrial rhythms during atrial fibrillation and atrial flutter, direction-dependent properties, and realistic anterograde and retrograde conduction curves in the control case and the cases of fast and slow pathway ablation. In addition, the model is accompanied by a visualization of electrical conduction in the AVN, revealing the interaction between fast and slow pathways in the form of ladder diagrams. To show the validity of the proposed model, we compare the simulation results with the available experimental data.
The proposed model can be used both as a stand-alone module and as a part of complex 3D atrial or whole heart simulation systems. The results were published in the journal "Frontiers in Physiology" (impact factor 4.755), and the MATLAB source code was placed in a public repository.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
In the process of developing the cardiac conduction system model, we faced difficulties building a realistic model of the AVN since it is the most complex and puzzling part of the cardiac conduction system. We managed to create a compact mathematical AVN model for rabbit heart with a dual pathway structure using our recently developed model (PLOS One, 17(4): e0257935, 2022) for the pacemaking variant of the two-variable excitable Aliev-Panfilov cardiac cell model. Our model is multifunctional and realistically reproduces the behavior of the rabbit AVN observed in experiments. The model is computationally lightweight and provides multiple unique functions, such as retrograde conduction and coupling asymmetry, not available in any other AVN models. Pertinent MATLAB software was developed.
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| Strategy for Future Research Activity |
Using computer simulations with our model of the rabbit AVN, we will explore some cardiac system phenomena such as atrioventricular reentrant tachycardia (AVNRT) and Wenckebach periodicity. We will continue to enhance the model of the cardiac conduction system creating simple models for cardiac muscles able to produce ECG signals. We will study the difference in origin of "typical" (slow pathway - fast pathway) and "atypical" (fast pathway - slow pathway) types of AVNRT. Also, we will explore the appearance of different Wenckebach patterns and the role of secondary AV nodal pacemaker in the Wenckebach pattern formation. For this purpose, additional MATLAB software will be developed, and corresponding computer simulations will be performed.
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