Polak Sebastian, Wiśniowska Barbara, Mendyk Aleksander, Pacławski Adam, Szlęk Jakub
Department of Pharmacoepidemiology and Pharmacoeconomics and Department of Social Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland.
Simcyp (a Certara Company) Limited, Blades Enterprise Centre, John Street, Sheffield S2 4SU, UK.
Comput Math Methods Med. 2018 Jan 4;2018:3719703. doi: 10.1155/2018/3719703. eCollection 2018.
Human heart electrophysiology is complex biological phenomenon, which is indirectly assessed by the measured ECG signal. ECG trace is further analyzed to derive interpretable surrogates including QT interval, QRS complex, PR interval, and T wave morphology. QT interval and its modification are the most commonly used surrogates of the drug triggered arrhythmia, but it is known that the QT interval itself is determined by other nondrug related parameters, physiological and pathological. In the current study, we used the computational intelligence algorithms to analyze correlations between various simulated physiological parameters and QT interval. Terfenadine given concomitantly with 8 enzymatic inhibitors was used as an example. The equation developed with the use of genetic programming technique leads to general reasoning about the changes in the prolonged QT. For small changes of the QT interval, the drug-related IKr and ICa currents inhibition potentials have major impact. The physiological parameters such as body surface area, potassium, sodium, and calcium ions concentrations are negligible. The influence of the physiological variables increases gradually with the more pronounced changes in QT. As the significant QT prolongation is associated with the drugs triggered arrhythmia risk, analysis of the role of physiological parameters influencing ECG seems to be advisable.
人体心脏电生理学是一种复杂的生物现象，通过测量的心电图信号进行间接评估。对心电图轨迹进行进一步分析，以得出可解释的替代指标，包括QT间期、QRS波群、PR间期和T波形态。QT间期及其变化是药物引发心律失常最常用的替代指标，但已知QT间期本身由其他与药物无关的生理和病理参数决定。在本研究中，我们使用计算智能算法来分析各种模拟生理参数与QT间期之间的相关性。以特非那定与8种酶抑制剂同时使用为例。利用遗传编程技术开发的方程可对QT延长的变化进行一般推理。对于QT间期的微小变化，与药物相关的IKr和ICa电流抑制电位具有主要影响。诸如体表面积、钾、钠和钙离子浓度等生理参数可忽略不计。随着QT变化更为明显，生理变量的影响逐渐增加。由于显著的QT延长与药物引发的心律失常风险相关，分析影响心电图的生理参数的作用似乎是可取的。
