R F Gilmour1, N S Moïse. 1. Departments of Physiology and Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401, USA.
Abstract
OBJECTIVES: This study sought to determine whether early afterdepolarization-induced triggered activity is responsible for the initiation of ventricular arrhythmias in dogs with an inherited predisposition to sudden death. BACKGROUND: We have identified a colony of German shepherd dogs that display inherited ventricular ectopic activity and sudden cardiac death. The arrhythmias in these animals are pause dependent but are not associated with a prolonged QT interval, suggesting that they might be initiated by early afterdepolarization-induced triggered activity in Purkinje fibers. METHODS: Cardiac Purkinje fibers obtained from dogs that either did or did not exhibit ventricular tachyarrhythmias at the time of study were superfused in vitro with normal Tyrode solution (extracellular potassium ion concentration 4 mmol/liter) and were studied using standard microelectrode techniques. RESULTS: Early afterdepolarizations and triggered activity occurred spontaneously in Purkinje fibers obtained from affected dogs (n = 7) but not in fibers obtained from unaffected dogs (n = 13). Exit conduction block of triggered responses occurred to varying degrees within the Purkinje fiber but not at the Purkinje-muscle junction. Overdrive pacing suppressed triggered activity. The reemergence of triggered activity after cessation of pacing was both time and rate dependent. Triggered activity in fibers obtained from affected dogs was potentiated by phenylephrine and epinephrine and was suppressed by isoproterenol. Triggered activity was not induced by phenylephrine or epinephrine in fibers obtained from unaffected dogs. CONCLUSIONS: These results support the hypothesis that early afterdepolarization-induced triggered activity in Purkinje fibers is responsible for the initiation of ventricular arrhythmias in this canine model of inherited sudden death.
OBJECTIVES: This study sought to determine whether early afterdepolarization-induced triggered activity is responsible for the initiation of ventricular arrhythmias in dogs with an inherited predisposition to sudden death. BACKGROUND: We have identified a colony of German shepherd dogs that display inherited ventricular ectopic activity and sudden cardiac death. The arrhythmias in these animals are pause dependent but are not associated with a prolonged QT interval, suggesting that they might be initiated by early afterdepolarization-induced triggered activity in Purkinje fibers. METHODS: Cardiac Purkinje fibers obtained from dogs that either did or did not exhibit ventricular tachyarrhythmias at the time of study were superfused in vitro with normal Tyrode solution (extracellular potassium ion concentration 4 mmol/liter) and were studied using standard microelectrode techniques. RESULTS: Early afterdepolarizations and triggered activity occurred spontaneously in Purkinje fibers obtained from affected dogs (n = 7) but not in fibers obtained from unaffected dogs (n = 13). Exit conduction block of triggered responses occurred to varying degrees within the Purkinje fiber but not at the Purkinje-muscle junction. Overdrive pacing suppressed triggered activity. The reemergence of triggered activity after cessation of pacing was both time and rate dependent. Triggered activity in fibers obtained from affected dogs was potentiated by phenylephrine and epinephrine and was suppressed by isoproterenol. Triggered activity was not induced by phenylephrine or epinephrine in fibers obtained from unaffected dogs. CONCLUSIONS: These results support the hypothesis that early afterdepolarization-induced triggered activity in Purkinje fibers is responsible for the initiation of ventricular arrhythmias in this canine model of inherited sudden death.
Authors: Daisuke Sato; Lai-Hua Xie; Ali A Sovari; Diana X Tran; Norishige Morita; Fagen Xie; Hrayr Karagueuzian; Alan Garfinkel; James N Weiss; Zhilin Qu Journal: Proc Natl Acad Sci U S A Date: 2009-02-13 Impact factor: 11.205