A novel method to quantify contribution of electrical restitution to alternans of repolarization in cardiac myocytes: A simulation study

There is evidence that alternans of repolarization, i.e. a beat to beat alternation in the action potential duration (APD), is a precursor to ventricular fibrillation. Electrical restitution is considered important in predicting the onset of alternans in cardiac myocytes. Restitution predicts action potential duration (APD) based on the preceding diastolic interval (DI). Determining how much restitution contributes to alternans is not possible with existing methods. We used mathematical models and control of DI using a novel pacing protocol to quantify DI dependent contribution to alternans. Using the canine ventricular model (CVM), we paced at one end of the simulated tissue and found the DI dependent contribution as a rate of increase in the amplitude of alternans as a function of tissue length. Through manipulation of different ionic currents, we compared the new method with standard and dynamic restitution to quantify the contribution of different ionic currents towards DI independent and dependent components. When the L‐type calcium current was altered, we found non‐conformal changes between standard restitution and our method at a controlled DI value of 30 msec. These results suggest that the new method allows for unmasking of features of mechanisms of alternans not seen with current methods. Supported by grant CBET 0730450 from the National Science Foundation.