Parameters

Various parameters are used in order to describe in silico cardiac safety profile of compounds:

Action potential duration (APD) and triangulation (T)

      APD is calculated at 40, 60 or 90 % (APD₄₀, APD₆₀ or APD ₉₀) of the action potential amplitude (APA)

      T₄₀ is calculated as the APD₉₀ - APD₄₀ 

      T₆₀ is calculated as the APD₉₀ - APD₆₀ 

Action potential duration increase or decrease (APD)

    APD is calculated as APD₉₀ in presence of compound - APD ₉₀ in absence of compound, for example

Early afterdepolarization

      EAD is defined as a increase of the membrane voltage during the AP phase 2

Transmural dispersion of repolarization (TDR)

    TDR is calculated as the difference between APD₉₀ measured on midmyocardial myocyte and APD₉₀ measured with epicardial myocyte

Reverse use dependence (RUD)

      Prolongation of APD is calculated in the presence or absence of compound at cycle lenght of 1000 (APD₉₀P₁₀₀₀) or 4000 ms (APD₉₀P₄₀₀₀)  observed on midmyocardial myocyte 

      RUD is calculated as the difference between APD₉₀P₄₀₀₀ and APD₉₀P₁₀₀₀

Minimal rate of AP decrease measured at EAD take off voltage (V_min)

     V_min is calculated as the minimal rate of AP decrease measured at the EAD take off voltage. 

      In the presence of an EAD, V_min is equal to zero.

      In absence of EAD, V_min represent the propensity of the compound to induce an EAD