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Atrial Infarction-Induced Spontaneous Focal Discharges and Atrial Fibrillation in Sheep

Overview of attention for article published in Circulation: Arrhythmia and Electrophysiology, March 2018
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Title
Atrial Infarction-Induced Spontaneous Focal Discharges and Atrial Fibrillation in Sheep
Published in
Circulation: Arrhythmia and Electrophysiology, March 2018
DOI 10.1161/circep.117.005659
Pubmed ID
Authors

Uma Mahesh R Avula, Jonathan J Hernandez, Masatoshi Yamazaki, Carmen R Valdivia, Antony Chu, Alvaro Rojas-Pena, Kuljeet Kaur, Roberto Ramos-Mondragón, Justus M Anumonwo, Stanley Nattel, Héctor H Valdivia, Jérôme Kalifa

Abstract

The mechanisms underlying spontaneous atrial fibrillation (AF) associated with atrial ischemia/infarction are incompletely elucidated. Here, we investigate the mechanisms underlying spontaneous AF in an ovine model of left atrial myocardial infarction (LAMI). LAMI was created by ligating the atrial branch of the left anterior descending coronary artery. ECG loop recorders were implanted to monitor AF episodes. In 7 sheep, dantrolene-a ryanodine receptor blocker-was administered in vivo during the 8-day observation period (LAMI-D, 2.5 mg/kg, IV, BID). LAMI animals experienced numerous spontaneous AF episodes during the 8-day monitoring period that were suppressed by dantrolene (LAMI, 26.1±5.1; sham, 4.3±1.1; LAMI-D, 2.8±0.8; mean±SEM episodes per sheep, P<0.01). Optical mapping showed spontaneous focal discharges (SFDs) originating from the ischemic/normal-zone border. SFDs were calcium driven, rate dependent, and enhanced by isoproterenol (0.03 µmol/L, from 210±87 to 3816±1450, SFDs per sheep) but suppressed by dantrolene (to 55.8±32.8, SFDs per sheep, mean±SEM). SFDs initiated AF-maintaining reentrant rotors anchored by marked conduction delays at the ischemic/normal-zone border. NOS1 (NO synthase-1) protein expression decreased in ischemic zone myocytes, whereas NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) oxidase and xanthine oxidase enzyme activities and reactive oxygen species (DCF [6-carboxy-2',7'-dichlorodihydrofluorescein diacetate]-fluorescence) increased. CaM (calmodulin) aberrantly increased [3H]ryanodine binding to cardiac RyR2 (ryanodine receptors) in the ischemic zone. Dantrolene restored the physiological binding of CaM to RyR2. Atrial ischemia causes spontaneous AF episodes in sheep, caused by SFDs that initiate reentry. Nitroso-redox imbalance in the ischemic zone is associated with intense reactive oxygen species production and altered RyR2 responses to CaM. Dantrolene administration normalizes the CaM response, prevents LAMI-related SFDs, and AF initiation. These findings provide novel insights into the mechanisms underlying ischemia-related atrial arrhythmias.

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Mendeley readers

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The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 29%
Student > Master 5 24%
Researcher 3 14%
Student > Bachelor 1 5%
Professor 1 5%
Other 0 0%
Unknown 5 24%
Readers by discipline Count As %
Medicine and Dentistry 4 19%
Biochemistry, Genetics and Molecular Biology 2 10%
Engineering 2 10%
Agricultural and Biological Sciences 1 5%
Physics and Astronomy 1 5%
Other 1 5%
Unknown 10 48%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 March 2018.
All research outputs
#14,393,794
of 25,382,440 outputs
Outputs from Circulation: Arrhythmia and Electrophysiology
#1,209
of 1,679 outputs
Outputs of similar age
#168,394
of 344,853 outputs
Outputs of similar age from Circulation: Arrhythmia and Electrophysiology
#42
of 54 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,679 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.8. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,853 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 54 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.