Dataset Information

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

ABSTRACT:

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) Ca(2+) release (Ca(2+) 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 (Ca(i)) 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 mumol/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 Ca(i) 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 Ca(2+) clock malfunction, characterized by unresponsiveness to isoproterenol and caffeine and down-regulation of RyR2 in SAN.

SUBMITTER: Joung B

PROVIDER: S-EPMC2925681 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Joung Boyoung B Lin Shien-Fong SF Chen Zhenhui Z Antoun Patrick S PS Maruyama Mitsunori M Han Seongwook S Piccirillo Gianfranco G Stucky Marcelle M Zipes Douglas P DP Chen Peng-Sheng PS Das Mithilesh Kumar MK

Heart rhythm 20090916 1

<h4>Background</h4>The mechanism of sinoatrial node (SAN) dysfunction in atrial fibrillation (AF) is unclear.<h4>Objective</h4>The purpose of this study was to test the hypothesis that defective spontaneous sarcoplasmic reticulum (SR) Ca(2+) release (Ca(2+) clock) is in part responsible for SAN dysfunction in AF.<h4>Methods</h4>Arrhythmic events and SAN function were evaluated in pacing-induced AF dogs (n = 7) and in normal dogs (n = 19) with simultaneous intracellular calcium (Ca(i)) and membra ...[more]

PMID: 19914141

Similar Datasets

Project description:ImportanceAtrial fibrillation (AF) can develop following thoracic irradiation. However, the critical cardiac substructure responsible for AF has not been properly studied.ObjectiveTo describe the incidence of AF in patients with lung cancer and determine predictive cardiac dosimetric parameters.Design, setting, and participantsThis retrospective cohort study was performed at a single referral center and included 239 patients diagnosed with limited-stage small cell lung cancer (SCLC) and 321 patients diagnosed with locally advanced non-small cell lung cancer (NSCLC) between August 2008 and December 2019 who were treated with definitive chemoradiotherapy.ExposuresRadiation dose exposure to cardiac substructures, including the chambers, coronary arteries, and cardiac conduction nodes, were calculated for each patient.Main outcomes and measuresMain outcomes were AF and overall survival.ResultsOf the 239 and 321 patients with SCLC and NSCLC, the median (IQR) age was 68 (60-73) years and 67 (61-75) years, and 207 (86.6%) and 261 (81.3%) were men, respectively. At a median (IQR) follow-up time of 32.7 (22.1-56.6) months, 9 and 17 patients experienced new-onset AF in the SCLC and NSCLC cohorts, respectively. The maximum dose delivered to the sinoatrial node (SAN Dmax) exhibited the highest predictive value for prediction of AF. A higher SAN Dmax significantly predicted an increased risk of AF in patients with SCLC (adjusted hazard ratio [aHR], 14.91; 95% CI, 4.00-55.56; P < .001) and NSCLC (aHR, 15.67; 95% CI, 2.08-118.20; P = .008). However, SAN Dmax was not associated with non-AF cardiac events. Increased SAN Dmax was significantly associated with poor overall survival in patients with SCLC (aHR, 2.68; 95% CI, 1.53-4.71; P < .001) and NSCLC (aHR, 1.97; 95% CI, 1.45-2.68; P < .001).Conclusions and relevanceIn this cohort study, results suggest that incidental irradiation of the SAN during chemoradiotherapy may be associated with the development of AF and increased mortality. This supports the need to minimize radiation dose exposure to the SAN during radiotherapy planning and to consider close follow-up for the early detection of AF in patients receiving thoracic irradiation.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets