Block of I-Ks does not induce early afterdepolarization activity but promotes beta-adrenergic agonist-induced delayed afterdepolarization activity

Block of I-kappa s Does Not Induce EADs. Introduction: An early afterdepola rization (EAD) induced triggered beat is thought to precipitate torsade de pointes (TdP) in the long QT syndrome (LQTS). Previous studies demonstrated the development of EAD activity and dispersion of repolarization under LQT 2 (reduced I-kappa r) and LQT3 (augmented late I-Na), but not LQT1 (reduced I-kappa s), conditions. The present study examines these electrophysiologi c characteristics during I-kappa s block. Methods and Results: Canine epicardial (Epi), M, and endocardial (Endo) tis sues and Purkinje fibers isolated from the canine left ventricle were studi ed using standard microelectrode recording techniques. The I-kappa s blocke r chromanol 293B (293B, 30 mu M), produced a homogeneous rate-independent p rolongation of action potential duration (APD) in Epi, M, and Endo, but lit tle to no APD prolongation in Purkinje, Chromanol 293B 1 to 30 mu M failed to induce EADs or delayed afterdepolarizations (DADs) in any of the four ti ssue types, Isoproterenol (ISO, 0.1 to 1.0 mu M) in the presence of 293B 30 mu M significantly prolonged the BPD of the hf cell (basic cycle length gr eater than or equal to 1 sec), abbreviated that of Purkinje, and caused lit tle change in that of Epi and Endo, The combination of 293B 30 mu M and ISO 0.2 mu M did not induce EADs in any of the four tissue types, but produced DAD activity in 4 of 8 Epi, 7 of 10 M cells, and 3 of 8 Endo. Conclusion: Our results indicate that I-kappa s block alone or in combinati on with beta-adrenergic stimulation does not induce EADs in any of the four canine ventricular tissue types, but that the combination of the two induc es DADs as well as accentuated dispersion of repolarization.