Pretreatment of BAPTA-AM Suppresses the Genesis of Repetitive Endocardial Focal Discharges and Pacing-Induced Ventricular Arrhythmia During Global Ischemia

BAPTA‐AM and Repetitive Endocardial Focal Discharges. Introduction: In isolated rabbit hearts, repetitive endocardial focal discharges (REFDs) were consistently observed during ventricular fibrillation (VF) with prolonged (>5 minutes) global ischemia (GI). We hypothesized that BAPTA‐AM, a calcium chelator, can suppress these REFDs. Methods and Results: Using a two‐camera optical mapping system, we simultaneously mapped endocardial (left ventricle, LV) and epicardial (both ventricles) activations during ventricular arrhythmia with GI. In 5 hearts (protocol I), we infused Tyrode's solution (no BAPTA‐AM) for ≥30 minutes before the onset of no‐flow GI. In 7 additional hearts (protocol II), BAPTA‐AM (20 μmol/L) was infused for ≥30 minutes before the initiation of GI. In protocol I, sustained VF (>30 seconds) was successfully induced in all 5 hearts with prolonged GI. REFDs were present in >85 % of recording time. In protocol II, however, ventricular arrhythmia was not inducible and REFDs were not observed after 5‐minute GI in 5 hearts. Effects of BAPTA‐AM on intracellular calcium (Cai) at the LV endocardium were also evaluated in 5 hearts (protocol III) using dual Cai/membrane potential mapping. GI, both without and with BAPTA‐AM pretreatment, caused a decrease of Cai amplitude during S1 pacing. However, this effect was more pronounced in the hearts with BAPTA‐AM pretreatment (P < 0.001). GI, without BAPTA‐AM pretreatment, caused broadening of Cai transient. In contrast, GI, with BAPTA‐AM pretreatment, caused narrowing of Cai transient. Conclusions: BAPTA‐AM pretreatment attenuates Cai transient, suppressing the genesis of REFDs and pacing‐induced ventricular arrhythmia during GI. These findings support the notion that Cai dynamics is important in the maintenance of REFDs. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1154‐1162, October 2011)