Mechanisms of sinoatrial node dysfunction in a canine model of pacing-induced atrial fibrillation

Boyoung Joung, Shien Fong Lin, Zhenhui Chen, Patrick S. Antoun, Mitsunori Maruyama, Seongwook Han, Gianfranco Piccirillo, Marcelle Stucky, Douglas P. Zipes, Peng Sheng Chen, Mithilesh Kumar Das

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Background: The mechanism of sinoatrial node (SAN) dysfunction in atrial fibrillation (AF) is unclear. Objective: The purpose of this study was to test the hypothesis that defective spontaneous sarcoplasmic reticulum (SR) Ca2+ release (Ca2+ clock) is in part responsible for SAN dysfunction in AF. Methods: Arrhythmic events and SAN function were evaluated in pacing-induced AF dogs (n = 7) and in normal dogs (n = 19) with simultaneous intracellular calcium (Cai) and membrane potential recording. Results: AF dogs had frequent sinus pauses during Holter monitoring. Isolated right atrium (RA) from AF dogs showed slower heart rate (P = .001), longer SAN recovery time (P = .001), and longer sinoatrial conduction time (P = .003) than normal. In normal RAs, isoproterenol 0.3 and 1 μmol/L increased heart rate by 96% and 105%, respectively. In contrast, in RAs from AF dogs, isoproterenol increased heart rate by only 60% and 72%, respectively. Isoproterenol induced late diastolic Cai elevation (LDCAE) at superior SAN in all 19 normal RAs but in only 3 of 7 AF RAs (P = .002). In AF RAs without LDCAE (n = 4), heart rate increased by the acceleration of ectopic foci. Caffeine (20 mmol/L) injection increased heart rate with LDCAE in all 6 normal RAs but did not result in LDCAE in any of the 5 AF RAs (P = .002). Type 2 ryanodine receptor (RyR2) in the superior SAN of AF dogs was decreased to 33% of normal (P = .02). Conclusion: SAN dysfunction in AF is associated with Ca2+ clock malfunction, characterized by unresponsiveness to isoproterenol and caffeine and down-regulation of RyR2 in SAN.

Original languageEnglish
Pages (from-to)88-95
Number of pages8
JournalHeart Rhythm
Issue number1
Publication statusPublished - 2010 Jan

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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