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Changes in Left Ventricular Repolarization and Ion Channel Currents Following a Transient Rate Increase Superimposed on Bradycardia in Anesthetized Dogs
Author(s) -
RUBART MICHAEL,
LOPSHIRE JOHN C.,
FINEBERG NAOMI S.,
ZIPES DOUGLAS P.
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.tb00028.x
Subject(s) - medicine , bradycardia , cardiology , repolarization , transient (computer programming) , ion channel , heart rate , benign early repolarization , increased heart rate , anesthesia , electrophysiology , blood pressure , st segment , myocardial infarction , receptor , computer science , operating system
Electrical Remodeling of the Heart due to Rate. Introduction: We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. Methods and Results: The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid‐myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by ∼6 and ∼3 mV, respectively (P < 0.02). and prolonged action potential duration at 90% repolarization from 235 ± 8 msec to 278 ± 8 msec (1 Hz; P = 0.02). Rapid pacing‐induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4‐aminopyridine‐sensitive transient outward K + current, I to over the range of physiologic frequencies, resulting from a ∼30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L‐type Ca 2+ currents, I ca.I.' by 15% to 35% between +10 and +60 mV; and (3) increases in peak density of the Ca 2+ ‐activated chloride current, I Cl.Ca' by 30% to 120% between +30 and +50 mV. Conclusion: Frequency‐dependent reduction in I to combined with enhanced I Ca.I. causes an increase in net inward current that may he responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward I Ca.Cl.