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Abstract 12789: Time-Dependent Changes in Mitochondrial Properties and Function in Dogs During Electrically Maintained Atrial Fibrillation

2022· article· en· W4380794748 on OpenAlexaff
Xiaoyan Qi, Jiening Xiao, Feng Xiong, Stanley Nattel

Bibliographic record

VenueCirculation · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicViral Infectious Diseases and Gene Expression in Insects
Canadian institutionsUniversité de MontréalMontreal Heart Institute
Fundersnot available
KeywordsMedicineAtrial fibrillationInternal medicineCalceinEndocrinologyCardiologyChemistryBiochemistry

Abstract

fetched live from OpenAlex

Introduction: Atrial fibrillation (AF) causes atrial remodeling, leading to progressive resistance to therapy. Changes in cell metabolism likely contribute to remodeling; here, we studied the nature and time course of mitochondrial (MITO) changes during AF . Methods: Atrial cardiomyocytes were isolated from control dogs and dogs kept in AF for 24 hrs, 3 days, 1 and 3 wks by atrial tachypacing at 600 bpm (N=10/group). MITO were visualized with transmission electron microscopy. [Ca 2+ ] Mito (Rhod-2 AM), MITO ROS production (MitoSOX), membrane potential (αψ, JC-1), mPTP opening (TMRM) and FAD autofluorescence were measured via confocal microscope, NADH autofluorescence was determined under UV light. Protein expression was assayed by western blotting. Results: MITO elongation occurred following 24-hr and 3-day AF, while 3-week AF induced MITO fragmentation, rupture and shrinking (A). MITO fusion protein (MFN1) decreased from 3 days to 3 wks of AF and fission protein pDRP1ser-616 was increased at 1 and 3 wks of AF, potentially accounting for MITO fragmentation. [Ca 2+ ] Mito increased progressively with AF-time (B). MITO ROS production increased at 24 hr AF, and remained elevated from 3 days to 3 wks of AF (C). SOD2 was reduced after 3 days AF. NOX4 expression was increased at 3 wks AF. mPTP opening frequency and duration increased progressively during AF (D). AF increased JC-1 fluorescence, indicating depolarized αψ, beginning 24 hours after AF-onset (E). NADH increased by 15% at 24 hr AF, and then decreased progressively with AF-time (F). FAD was decreased during AF. Mitotempo (5-μM) reversed AF-induced atrial-cell I CaL downregulation (G) and reduced triggered activity (H). Conclusions: MITO are activated early during AF, but then show progressive changes likely due to ROS autotoxicity. MITO dysfunction and impaired bioenergetics may contribute to AF maintenance/ progress. MITO-targeted antioxidant intervention may have potential as a novel therapeutic approach for AF.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.218
Teacher spread0.208 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2022
Admission routes1
Has abstractyes

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