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Delayed afterdepolarization in intact canine sinoatrial node as a novel mechanism for atrial arrhythmia

Authors
 Boyoung Joung  ;  Hong Zhang  ;  Tetsuji Shinohara  ;  Mitsunori Maruyama  ;  Seongwook Han  ;  Daehyeok Kim  ;  Eue-Keun Choi  ;  Young-Keun On  ;  Shien-Fong Lin  ;  Peng-Sheng Chen 
Citation
 JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Vol.22(4) : 448-454, 2011 
Journal Title
 JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY 
ISSN
 1045-3873 
Issue Date
2011
MeSH
Action Potentials/drug effects ; Action Potentials/physiology* ; Animals ; Arrhythmias, Cardiac/chemically induced ; Arrhythmias, Cardiac/physiopathology* ; Atrial Function, Right/drug effects ; Atrial Function, Right/physiology* ; Dogs ; Heart/drug effects ; Heart/physiology* ; Heart Rate/drug effects ; Heart Rate/physiology* ; Isoproterenol/toxicity ; Membrane Potentials/drug effects ; Membrane Potentials/physiology ; Sinoatrial Node/drug effects ; Sinoatrial Node/physiology* ; Time Factors
Keywords
afterdepolarization ; calcium dynamics ; sinoatrial node ; sympathetic nervous system ; triggered activity
Abstract
INTRODUCTION: Recent evidence indicates that spontaneous sarcoplasmic reticulum Ca release and Na-Ca exchanger current activation contribute to the sinoatrial node (SAN) automaticity. These findings suggest that SAN activity may share mechanisms that underlie both automaticity and triggered activity. The aim of this study is to test the hypothesis that spontaneous, nonvoltage gated, intracellular Ca (Ca(i)) elevation may induce delayed afterdepolarization (DAD) in intact SAN during isoproterenol infusion. METHODS AND RESULTS: We simultaneously mapped Ca(i) and membrane potential in 31 isolated Langendorff-perfused canine right atriums (RA). Isoproterenol increased heart rate and late diastolic Ca(i) elevation (LDCAE) of the superior SAN, leading to consistent SAN automaticity in all 31 RAs. However, DAD-like diastolic depolarizations (DD) were transiently observed in 4 RAs during isoproterenol infusion. These DAD-like DDs were preceded by LDCAE, but did not trigger a full action potential. The LDCAE preceding DAD-like DDs had smaller amplitude (0.41 ± 0.08 AU vs 0.48 ± 0.07 AU, P = 0.001) and less steep slopes (3.7 ± 1.3 AU/s vs 4.8 ± 1.4 AU/s, P = 0.001) than that of sinus beats. The coupling interval of DAD-like DDs was longer than that of the preceding normal beats (407 ± 48 ms vs 371 ± 44 ms, P = 0.002). CONCLUSION: The isoproterenol-induced LDCAE of superior SAN induced a full action potential in most cases. However, if the LDCAE was too small to trigger an action potential, then it induces only DAD-like DD. The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis.
Files in This Item:
T201101857.pdf Download
DOI
10.1111/j.1540-8167.2010.01905.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/93379
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