Session S23.4

Adaptation of an Action Potential Minimal Model to Acute Ischemia

F Gasperini, C Lamberti, JM Ferrero*

Universidad Politecnica de Valencia
Valencia, Spain

Dynamic, last generation action potential models, such as the Ten Tusscher model or the Rudy models, are capable of reproducing normal and pathological (e.g. ischemic) action potentials with a high degree of electro-physiological detail. However, they can become extremely computationally expensive when used in large scale simulations (i.e. when simulating the electrical activity of a 3D geometrically realistic heart). Conversely, phenomenological (“minimal”) models of cardiac action potential (e.g. the Fenton-Karma model) are less realistic but also less mathematically complex, thus resulting in much faster simulations when used in a 3D virtual heart. However, the electrophysiological simplifications inherent to these models (e.g. the non-existence of individual realistic ionic currents) jeopardizes their usefulness to simulate cardiac pathologies.
The aim of this work is to investigate the validity of a Fenton-Karma-based minimal model (the Bueno 2007 model) to reproduce myocardial ischemia at the cellular level. For this purpose, we modified the model by introducing a new current Isoi=Gsoi*(u-Esoi) (mimicking the ATP-sensitive potassium current) with the intention of provoking changes in the action potential similar to those found in ischemia, and also introducing a smooth voltage-dependence (using a Hill-type function of exponent H) in the fast inward current inactivation gate (v) of the model in order to set the stage for postrepolarization refractoriness, another characteristic feature of ischemia.
We monitored the action potential duration (APD), action potential amplitude (APA), resting membrane potential (RP) and effective refractory period (ERP) for different values of Gsoi and Esoi, the different values of these parameters mimicking the time-course of acute ischemia. For H=2, APD was reduced from 280 milliseconds in control conditions to 174 milliseconds after 5 minutes of ischemia (from 260 to 169 milliseconds for H=5), and to 130 milliseconds after 10 minutes of ischemia (131 milliseconds for H=5), which correspond to realistic values of ischemic APDs. As for the RP, it increased from 0.001 to 0.006 (arbitrary units) after 10 minutes of ischemia regardless of the value of H. APA also changed as expected (reducing its value from 1.5 to 1.48, arbitrary units). However, postrepolarization refractoriness could not be correctly reproduced regardless of the values of the ischemic parameters.
In conclusion, the Bueno model is capable of correctly reproducing the ischemic changes in action potential morphology but not changes in excitability, which makes it useful for reproducing periodic non reentrant electrical activity in 3D virtual hearts.

(Abstract Control Number: 92)