RATIONALE: 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). METHODS AND 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.
RATIONALE: 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). METHODS AND 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: Mark Warren; Prabal K Guha; Omer Berenfeld; Alexey Zaitsev; Justus M B Anumonwo; Amit S Dhamoon; Suveer Bagwe; Steven M Taffet; José Jalife Journal: J Cardiovasc Electrophysiol Date: 2003-06
Authors: Michel Haïssaguerre; Morio Shoda; Pierre Jaïs; Akihiko Nogami; Dipen C Shah; Josef Kautzner; Thomas Arentz; Dietrich Kalushe; Dominique Lamaison; Mike Griffith; Fernando Cruz; Angelo de Paola; Fiorenzo Gaïta; Mélèze Hocini; Stéphane Garrigue; Laurent Macle; Rukshen Weerasooriya; Jacques Clémenty Journal: Circulation Date: 2002-08-20 Impact factor: 29.690
Authors: Louise Reilly; Francisco J Alvarado; Di Lang; Sara Abozeid; Hannah Van Ert; Cordell Spellman; Jarrett Warden; Jonathan C Makielski; Alexey V Glukhov; Lee L Eckhardt Journal: Circ Arrhythm Electrophysiol Date: 2020-08-04
Authors: Ling Xiao; Tamara T Koopmann; Balázs Ördög; Pieter G Postema; Arie O Verkerk; Vivek Iyer; Kevin J Sampson; Gerard J J Boink; Maya A Mamarbachi; Andras Varro; Luc Jordaens; Jan Res; Robert S Kass; Arthur A Wilde; C R Bezzina; Stanley Nattel Journal: Circ Res Date: 2013-03-26 Impact factor: 17.367