What Type of Drug Would be Antiarrhythmic in Acute Myocardial Ischemia? Insights from Simulations

Acute myocardial ischemia (AMI) can lead to life-threatening arrhythmias. Hyperkalemia is a major contributing factor, increasing the risk of unidirectional block and re-entry. It also causes dynamic changes in the shape of the action potential, along with acidosis and anoxia. During the AMI process, this heterogeneity creates a vulnerable window (VW) in which reentry may arise due to an ectopic stimulus. Nevertheless, there is no drug with specific purpose to target the electrophysiological and arrhythmogenic outcomes of AMI. Based on our previous research, an ideal drug with calcium channel blocker properties could be effective. Hence, this study aims to assess the impact of calcium channel blockade on the efficacy of drugs in reducing VW and preventing arrhythmias during AMI using 3D computational simulations. A modified version of the O'Hara et al. computational model was used to include the effects of AMI and drugs. Simulations were carried out on a biventricular 3D anatomical model including a realistic shape of the ischemic and border zone, transmural heterogeneity, and anisotropy. The results suggest a biphasic behavior of calcium blockade on VWs: moderate-low or high blockade prevents arrhtyhmias, whereas low or medium-high blockade exacerbates them. Control Reentrant Probability Index (RPI) is X whereas a RPI of T, Q, Y, and Z is observed at calcium blocking percentages of 20%, 40%, 60%, and 80% respectively. In conclusion, this study demonstrates the feasibility of insilica experiments for classify and test the drug efficacy in reducing susceptibility to arrhythmias in AMI.