title: A note on a method for determining advantageous properties of an anti-arrhythmic drug based on a mathematical model of cardiac cells.
abstract: Regional hyperkalemia during acute ischemia may provoke cardiac arrhythmias such as ventricular fibrillation. Despite intense research efforts over the last decades, the problem of finding an efficient anti-arrhythmic drug without dangerous side effects is still open. One approach to analyze the effect of anti-arrhythmic drugs is to do simulations based on mathematical models of collections of cardiomyocytes. Such simulations have recently illuminated the pro-arrhythmic capability of well-established anti-arrhythmic drugs. The purpose of the present note is to introduce a method intended for computing advantageous properties of an anti-arrhythmic drug. For a given model of a normal and an ischemic cell, we introduce a drug as a vector of non-negative real numbers whose components are multiplied by individual terms representing specific ionic currents. The drug vector is computed such that the action potentials of the resulting drugged cells are as close as possible to the action potential of a normal (not drugged) cell. Numerical simulations based on the Luo-Rudy I model and the Hund-Rudy model show that the classical shortened action potential obtained due to hyperkalemia is prolonged by using the drug computed by this method. Furthermore, for both models a 2D collection of spatially coupled ischemic cells give arrhythmogenic solutions before the drug is applied, and stable solutions after the drug is applied. It is emphasized that we do not address the possibility of realizing a drug with the properties computed in this note.
authors.affiliation: Simula Research Laboratory, 1325 Lysaker, Norway. aslak@simula.no
authors.forename: Aslak
authors.initials: A
authors.lastname: Tveito
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Lines
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003198:Computer Simulation; D006801:Humans; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents