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Block of I Ks Does Not Induce Early Afterdepolarization Activity but Promotes β‐Adrenergic Agonist‐Induced Delayed Afterdepolarization Activity
Author(s) -
BURASHNTKOV ALEXANDER,
ANTZELEVITCH CHARLES
Publication year - 2000
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2000.tb00342.x
Subject(s) - afterdepolarization , purkinje fibers , medicine , repolarization , ventricle , torsades de pointes , blockade , long qt syndrome , cardiology , endocrinology , qt interval , electrophysiology , receptor
Block of I K Does Not Induce EADs.Introduction : An early afterdepolarization (EAD)‐induced triggered heat 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 LQT2 (reduced I Kr ) and LQT3 (augmented late I Na ). but not LQTl (reduced I Ks ), conditions. The present study examines these electrophysiologic characteristics during I Ks block. Methods and Results : Canine epicardial (Epi), M, and endocardial (Endo) tissues and Purkinje fibers isolated from the canine left ventricle were studied using standard microelectrode recording techniques. The I Ks blocker chromanol 293B (293B, 30 μM), produced a homogeneous rate‐independent prolongation of action potential duration (APD) in Epi, M, and Endo, but little to no APD prolongation in Purkinje. Chromanol 293B I to 30 μM failed to induce EADs or delayed afterdepolarizations (DADs) in any of the four tissue types. Isoproterenol (ISO, 0.1 to 1.0 μM) in the presence of 293B 30 μM significantly prolonged the APD of the M cell (basic cycle length ≥ sec), abbreviated that of Purkinje, and caused little change in that of Epi and Endo. The combination of 293B 30 μM and ISO 0.2 μM 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 Ks block alone or in combination with β‐adrenergic stimulation does not induce EADs in any of the four canine ventricular tissue types, but that the combination of the two induces DADs as well as accentuated dispersion of repolarization.