title: Diastolic intracellular calcium-membrane voltage coupling gain and postshock arrhythmias: role of purkinje fibers and triggered activity.
abstract: BACKGROUND
  Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome.
  
  
  OBJECTIVE
  We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (V(m)) to elevated intracellular calcium (Ca(i)) (high diastolic Ca(i)-voltage coupling gains).
  
  
  RESULTS
  We simultaneously mapped Ca(i) and V(m) on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca(i) elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 micromol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 mumol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Ca(i)-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). I(K1) suppression with CsCl (5 mmol/L, n=3), BaCl(2) (3 micromol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca(i)-voltage coupling gain and enabled epicardium to also generate TAs.
  
  
  CONCLUSIONS
  Higher diastolic Ca(i)-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. I(K)(1) is a major factor that determines the diastolic Ca(i)-voltage coupling gain.
authors.affiliation: Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Maruyama
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Shinohara
authors.forename: Young-Keun
authors.initials: YK
authors.lastname: On
authors.forename: Seongwook
authors.initials: S
authors.lastname: Han
authors.forename: Eue-Keun
authors.initials: EK
authors.lastname: Choi
authors.forename: Dae-Hyeok
authors.initials: DH
authors.lastname: Kim
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shen
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D017609:Barium Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003971:Diastole; D004594:Electrophysiology; D004699:Endocardium / Q000378:metabolism / Q000503:physiopathology; D056149:Epicardial Mapping; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010496:Pericardium / Q000378:metabolism / Q000503:physiopathology; D011188:Potassium / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D011817:Rabbits
chemical_list: D017609:Barium Compounds; D002316:Cardiotonic Agents; D002712:Chlorides; C024986:barium chloride; D002586:Cesium; C028019:cesium chloride; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium