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Early Afterdepolarizations Produced by d,1‐Sotalol and Clofilium
Author(s) -
PATTERSON EUGENE,
SCHERLAG BENJAMIN J.,
LAZZARA RALPH
Publication year - 1997
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.1540-8167.1997.tb01830.x
Subject(s) - afterdepolarization , bay k8644 , sotalol , stimulation , medicine , nifedipine , pharmacology , endocrinology , calcium , electrophysiology , repolarization , atrial fibrillation
EAD Formation by Class III Drugs. Introduction: The roles for L‐type calcium current and Na‐Ca exchange in early afterdepolarizations (EADs) attending d, l‐sotalol and clofilium were examined in canine Purkinje fibers and in enzymatically dispersed myocytes from canine subepicardium. Methods and Results: Spontaneous EADs were compared to EAD formation potentiated by stimulation of Na‐Ca exchange and facilitation of I Ca‐L (Bay K8644). Bay K8644 (10 ‐8 M) and stimulation of Na‐Ca exchange potentiated bradycardia‐dependent EADs. Stimulation of Na‐Ca exchange in Pnrkinje fibers pretreated with d, l‐sotalol (10 ‐5 M) and clofilium (10 ‐7 M) induced EADs at takeoff potentials negative (‐63 ± 4 and ‐62 ± 4 mV, respectively) to EADs potentiated by Bay K8644 (10 ‐8 M) (‐33 ± 2 and ‐34 ± 2 mV, respectively, P < 0.05), or EADs induced by Bay K8644 alone (10 ‐6 M) (‐31 ± 5 mV). In myocytes, Bay K8644 (10 ‐8 M) potentiated EADs in d, l‐sotalol‐ (10 ‐6 to 10 ‐4 M) or clofilium‐treated (10 ‐9 to 10 ‐7 M) cells at reduced potentials (‐10 ± 3 and ‐10 ± 4 mV, respectively) compared to EADs elicited by clofilium or d, l‐sotalol alone (‐25 ± 3 and ‐24 ± 3 mV, respectively), or stimulation of Na‐Ca exchange in the presence of d, l‐sotalol or clofilium (‐26 ± 4 and ‐26 ± 4 mV, respectively). Spontaneous EADs or EADs elicited by stimulation of Na‐Ca exchange coincident with drug treatment were suppressed by increasing Ca o 2+ but were not suppressed by nifedipine (10 ‐7 M). Conclusion: EADs elicited by d, l‐sotalol and clolllium in canine Purkinje tissue and epicardial myocytes are dependent upon Na‐Ca excbange rather than I Ca‐L “window current.”