Session S62.4

Relationship between the Potassium Currents Block and the Occurrence of Early after Depolarizations in the Setting of Sodium Current Blockade

T Moukabary*, DE Haines

William Beaumont Hospital
Royal Oak, MI, USA

Introduction: The blockade of the inward sodium current (INa), rapidly activating potassium current (IKr) and the slowly activating potassium current (IKs) is commonly seen in the clinical setting. The combined blockade may result in early after depolarizations (EADs) and clinical ventricular arrhythmias.
Hypothesis: We sought to model different degrees blockade of the IKr and IKs in the setting of mild to moderate INa blockade and to study its relationship to the induction of EADs.
Methods: We used a Pentium core duo IBM-Lenovo Thinkpad X60 laptop and the cese 1.4.5 platform (from http://cese.sourceforge.net/) to run Luo-Rudy Model II of mammalian ventricular action potential. We matched temperature, serum sodium, and serum potassium to those commonly seen in the clinical settings. We applied a range of blockade levels to the INa (scaling factor of 50-100%, corresponding to 50% blockade to no-blockade). Then we paced the cell for 5 minutes at a cycle length of 2000 ms to reach steady state before each adjustment of the scaling factors for the IKr or IKs. We adjusted the blockade scale of each current by steps of 1-10% and looked for occurrence of EADs.
Results: At each level of blockade of IKs there was a “critical level” of blockade of IKr after which the EADs started occurring and vice versa. At a scaling factor of 50% for the INa and 7% for IKs, EADs occurred regardless of the IKr blockade. However, with the same INa blockade and at a scaling factor of 55% for IKs, a complete blockade of IKr (i.e. scaling factor of 0%) was needed to induce EADs. When there was no blockade to the INa, EADs occurred at IKs scale of 7.5% regardless of IKr and a complete IKr blockade was needed to induce EADs when IKs was 30%.
Conclusion: At mild to moderate levels of INa blockade there is a linear relationship between the minimum levels of IKs and IKr blockade at which EADs occur. When INa is blocked, EADs needed lesser degree of potassium currents blockade to occur.

(Abstract Control Number: 142)