Simulation Study of the Protective Effect of Drugs in Acute Myocardial Ischemia.

Increased extracellular potassium concentration (hyperkalemia) and electrical alternans in the action potential (AP) have been shown experimentally to be highly proarrhythmic during the acute phase of myocardial ischemia (AMI), which is a leading cause of death worldwide. However, there is no drug specifically designed to effectively address the electrophysiological and arrhythmogenic consequences of AMI In this work, computational simulations have been used to study the efficacy of 95 drugs against arrhythmias of ischemic origin. A modified version of the O'Hara et al. computational model has been used to simulate the AMI and the effect of the drug at the cellular level. After defining a series of biomarkers and classification criteria, the results indicate that such classification is possible and Nitrendipine is determined as the most promising drug, standing out for its ability to establish hyperkalemic and electrical conditions compatible with an anti-arrhythmic tendency in all the biomarkers defined. In conclusion, the work demonstrates the feasibility of in-silico experiments to perform a classification capable of minimizing the vulnerability to arrhythmias in AMI.