Journal of Biomedical Engineering Research (대한의용생체공학회:의공학회지)

The Korean Society of Medical and Biological Engineering (대한의용생체공학회)
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Sensitivity Analysis of dVm/dtMax_repol to Ion Channel Conductance for Prediction of Torsades de Pointes Risk

다형 심실빈맥의 예측을 위한 dVm/dtMax_repol의 이온채널 전도도에 대한 민감도 분석

  • Jeong, Da Un (Department of IT Convergence Engineering, Kumoh National Institute of Technology) ;
  • Yoo, Yedam (Department of IT Convergence Engineering, Kumoh National Institute of Technology) ;
  • Marcellinus, Aroli (Department of IT Convergence Engineering, Kumoh National Institute of Technology) ;
  • Lim, Ki Moo (Department of IT Convergence Engineering, Kumoh National Institute of Technology)
  • 정다운 (IT융복합공학과 금오공과대학교) ;
  • 유예담 (IT융복합공학과 금오공과대학교) ;
  • ;
  • 임기무 (IT융복합공학과 금오공과대학교)
  • Received : 2022.08.29
  • Accepted : 2022.10.20
  • Published : 2022.10.31
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Abstract

Early afterdepolarization (EAD), a significant cause of fatal ventricular arrhythmias including Torsade de Pointes (TdP) in long QT syndromes, is a depolarizing afterpotential at the plateau or repolarization phase in action potential (AP) profile early before completing one pace. AP duration prolongation is related to EAD but is not necessarily accounted for EAD. Several computational studies suggested EAD can form from an abnormality in the late plateau and/or repolarization phase of AP shape. In this sense, we hypothesized the slope during repolarization has the characteristics to predict TdP risk, mainly focusing on the maximum slope during repolarization (dVm/dtmax_repol). This study aimed to predict the sensitivity of dVm/dtmax_repol to ion channel conductances as a TdP risk metric through a population simulation considering multiple effects of simultaneous reduction in six ion channel conductances of gNaL, gKr, gKs, gto, gK1, and gCaL. Additionally, we verified the availability of dVm/dtmax_repol for TdP risk prediction through the correlation analysis with qNet, the representative TdP metric. We performed the population simulations based on the methodology of Gemmel et al. using the human ventricular myocyte model of Dutta et al. Among the sixion channel conductances, dVm/dtmax_repol and qNet responded most sensitively to the change in gKr, followed by gNaL. Furthermore, dVm/dtmax_repol showed a statistically significant high negative correlation with qNet. The dVm/dtmax_repol values were significantly different according to three TdP risk levels of high, intermediate, and low by qNet (p<0.001). In conclusion, we suggested dVm/dtmax_repol as a new biomarker metric for TdP risk assessment.

Keywords

Acknowledgement

본 연구는 식품의약품안전처(22213MFDS3922)와 한국연구재단 이공학기초연구사업(2022R1A2C2006326), 과학기술정보통신부 및 정보통신기획평가원의 지역지능화혁신인재양성(Grand ICT연구센터) 사업의 연구결과로 수행되었음(IITP-2022-2020-0-01612).

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