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다형 심실빈맥의 예측을 위한 dVm/dt<sub>Max_repol</sub>의 이온채널 전도도에 대한 민감도 분석
정다운,유예담,임기무,Jeong, Da Un,Yoo, Yedam,Marcellinus, Aroli,Lim, Ki Moo 대한의용생체공학회 2022 의공학회지 Vol.43 No.5
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/dt<sub>max_repol</sub>). This study aimed to predict the sensitivity of dVm/dt<sub>max_repol</sub> 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 g<sub>NaL</sub>, g<sub>Kr</sub>, g<sub>Ks</sub>, g<sub>to</sub>, g<sub>K1</sub>, and g<sub>CaL</sub>. Additionally, we verified the availability of dVm/dt<sub>max_repol</sub> 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/dt<sub>max_repol</sub> and qNet responded most sensitively to the change in g<sub>Kr</sub>, followed by g<sub>NaL</sub>. Furthermore, dVm/dt<sub>max_repol</sub> showed a statistically significant high negative correlation with qNet. The dVm/dt<sub>max_repol</sub> 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/dt<sub>max_repol</sub> as a new biomarker metric for TdP risk assessment.