title: Pretreatment of BAPTA-AM suppresses the genesis of repetitive endocardial focal discharges and pacing-induced ventricular arrhythmia during global ischemia.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan. tjwu@vghtc.vghtc.gov.tw
authors.forename: Tsu-Juey
authors.initials: TJ
authors.lastname: Wu
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Tung-Chao
authors.initials: TC
authors.lastname: Lin
authors.forename: Jiunn-Cherng
authors.initials: JC
authors.lastname: Lin
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Ting
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D002614:Chelating Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004562:Electrocardiography; D004699:Endocardium / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005583:Fourier Analysis; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D010477:Perfusion; D011817:Rabbits; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D000889:Anti-Arrhythmia Agents; D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid