Determining the effects of memory and action potential duration alternans on cardiac restitution using a constant-memory restitution protocol.

Restitution, the dependence of action potential duration (APD) on diastolic interval, may be causally linked to the vulnerability of cardiac tissue to certain types of arrhythmias. While a number of pacing protocols are commonly used to quantify the restitution relation, one of these, the dynamic protocol, may result in the occurrence of APD alternans. However, the effects of APD alternans, and the concomitant alternation in cardiac memory, on the restitution curve are currently not well understood. Alternans preceding a given action potential may cause that action potential to have a different duration from one preceded by action potentials of identical duration. This interaction of alternans and memory can result in a dynamic restitution curve that is not unique. To address this, we have developed a constant-memory restitution protocol that enables the experimenter or modeller to obtain unique, constant-memory restitution curves at all diastolic intervals. Using this protocol, we obtained unique restitution curves for two ionic models of the cardiac action potential in the absence of alternans at all diastolic intervals. A comparison of the unique constant-memory and non-unique dynamic restitution curves for the two models shows that the presence of alternans can significantly alter the shape of the restitution curve compared to when alternans is absent.