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  • Title: Pretreatment of BAPTA-AM suppresses the genesis of repetitive endocardial focal discharges and pacing-induced ventricular arrhythmia during global ischemia.
    Author: Wu TJ, Lin SF, Hsieh YC, Lin TC, Lin JC, Ting CT.
    Journal: J Cardiovasc Electrophysiol; 2011 Oct; 22(10):1154-62. PubMed ID: 21489030.
    Abstract:
    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 (Ca(i) ) at the LV endocardium were also evaluated in 5 hearts (protocol III) using dual Ca(i) /membrane potential mapping. GI, both without and with BAPTA-AM pretreatment, caused a decrease of Ca(i) amplitude during S(1) 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 Ca(i) transient. In contrast, GI, with BAPTA-AM pretreatment, caused narrowing of Ca(i) transient. CONCLUSIONS: BAPTA-AM pretreatment attenuates Ca(i) transient, suppressing the genesis of REFDs and pacing-induced ventricular arrhythmia during GI. These findings support the notion that Ca(i) dynamics is important in the maintenance of REFDs. 
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