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APD, QT interval and Tx Values

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APD, QT interval and Tx Values

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Saiz Rodríguez, FJ.; Sanz I Carreras, F.; Pastor Maeso, M.; Trénor Gomis, BA.; Gomis-Tena Dolz, J.; Cano García, J.; Romero Pérez, L. (2017). APD, QT interval and Tx Values. https://doi.org/10.4995/Dataset/10251/90297

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Title: APD, QT interval and Tx Values
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UPV Unit: Universitat Politècnica de València. Centro de Investigación e Innovación en Bioingeniería
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Abstract:
This repository contains four Excel 2017 files named “APD.xlsx”, “QT.xlsx”, “Tx_APD.xlsx” and “Tx_QT.xlsx”. APD.xlsx and Tx_APD.xlsx files contain three sheets (called “Epi”, “Mid” and “Endo”), whereas the rest contain ...[+]
Subjects: QT prolongation , Drug-induced long-QT syndrome , QT , APD
Copyrigths: Reconocimiento - No comercial (by-nc)
DOI: 10.4995/Dataset/10251/90297
Description: Every sheet in described files contains a table of numbers (doubles), resulting from the transformation of a three-dimensional matrix. To do so, the first two columns and the first row of each table contain the Coordinates x, y and z of the original matrix respectively (no units). They range from -3 to 1 for the x and y axis (first and second column) and from -3 to 0 for the z axis (first row). The nature of the remaining numbers differs between files: APD.xlsx contains the Action Potential Duration at 90% repolarization (APD90) values in milliseconds, QT.xlsx contains QT interval durations in milliseconds, Tx_APD.xlsx contains Tx values calculated from the tables in APD.xlsx and Tx_QT.xlsx contains Tx values calculated from the table in QT.xlsx. Coordinates were calculated as the logarithm of the ratio of a drug concentration (C) over the concentration that is required to inhibit a 50% of a given ion channel current (Half inhibitory concentration or IC50). They represent the block effect of such drug on three main currents which control the Action Potential shape and duration, namely, the rapid component of the potassium delayed rectifier current (IKr), the slow component of the potassium delayed rectifier current (IKs) and the calcium type L current (ICaL). The following formulae can be used to deduce mentioned Coordinates: x = log_10(C/(IC_50 (I_Kr))) ; y = log_10(C/(IC_50 (I_Ks ) )); z = log_10(C/(IC_50 (I_CaL))). These are indeed part of the Hill equation (Hill coefficient set to 1), where G is the channel’s resulting conductance and G0 is the channel’s control conductance: G_[x || y || z] = G_0·1/(1+C/(IC_(50, [x || y || z] ) )) = G_0·1/(1+10^([x || y || z]) ). Conductances of the three main currents are thus translated into cardiac cellular or tissue models to study the effect of a wide range of drug concentrations. The following parameters were obtained and summarized in currently described files. 1. APD90 values were obtained through simulation of the electrical activity of a single cardiac ventricular cell using the most up-to-date available model, the O’Hara Rudy Model (ORd) [1]. It can simulate the activity of three cell types, located in different layers of the human heart. Sheets included in APD.xlsx and Tx_APD.xlsx files (Endo, Mid and Epi) correspond to Endocardial, Mid-myocardial and Epicardial cells simulations using the respective Ord single cell models. 2. QT values were obtained through simulation of the activity of a cardiac transmural strand of 165 cells (60 Endo, 45 Mid and 60 Epi cells) as described in O’Hara et al. 2011 [1]. 3. Tx is a new index presented in Romero et al. 2017 [2] for assessing drug cardiac safety in the early stages of development. It was calculated as the ratio of a drug concentration that produced a 10% prolongation of the APD or QT intervals (D10) over the drug’s Effective Free Therapeutic Plasma Concentration (EFTPC), and thus has no units. Detailed methods of the performed simulations, as well as Tx calculation, can be consulted in [2].
Type: Dataset

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