Drugs and choice of doses
Molecules were purchased from Abcam Biochemicals (Abcam Biochemicals, Cambridge, United Kingdom), Biotrend (BioTREND, Chemikalien GmbH, Koln, Germany), Carbosynth (Carbosynth Ltd, Berkshire, United Kingdom), Clinisciences (CliniSciences, Nanterre, France), Sequoia Research Product ltd (Sequoia Research Products, Pangbourne, United Kingdom) and Sigma-Aldrich (Saint Quentin, France). The list of pharmacological agents used for validation of the pulse contour model is provided in Supplemental Material 1, Table 1. The full list of tested drugs including suppliers, vehicles and volumes of administration depending on dose levels and route administration is provided in Supplemental Material 2, Table 2. Doses were selected from preliminary trials to determine the minimum effective dose causing either QTc prolongation, increase in HFQT oscillations or change in autonomic control. A set of experiments were also conducted at higher doses with dofetilide, moxifloxacin, quinidine, sotalol and thioridazine.