Pro-arrhythmic role of adrenergic spatial densities in the human atria: An in-silico study
Bibliographic record
Abstract
Chronic stress among young patients (≤ 45 years old) could result in autonomic dysfunction. Autonomic dysfunction could be exhibited via sympathetic hyperactivity, sympathetic nerve sprouting, and diffuse adrenergic stimulation in the atria. Adrenergic spatial densities could alter atrial electrophysiology and increase arrhythmic susceptibility. Therefore, we examined the role of adrenergic spatial densities in creating arrhythmogenic substrates in silico. We simulated three 25 cm2 atrial sheets with varying adrenergic spatial densities (ASD), activation rates, and external transmembrane currents. We measured their effects on spatial and temporal heterogeneity of action potential durations (APD) at 50% and 20%. Increasing ASD shortens overall APD, and maximum spatial heterogeneity (31%) is achieved at 15% ASD. The addition of a few (5% to 10%) adrenergic elements decreases the excitation threshold, below 18 μA/cm2, while ASDs greater than 10% increase their excitation threshold up to 22 μA/cm2. Increase in ASD during rapid activation increases APD50 and APD20 by 21% and 41%, respectively. Activation times of captured beats during rapid activation could change by as much as 120 ms from the baseline cycle length. Rapidly activated atrial sheets with high ASDs significantly increase temporal heterogeneity of APD50 and APD20. Rapidly activated atrial sheets with 10% ASD have a high likelihood (0.7 ± 0.06) of fragmenting otherwise uniform wavefronts due to the transient inexcitability of adrenergically stimulated elements, producing an effective functional block. The likelihood of wave fragmentation due to ASD highly correlates with the spatial variations of APD20 (ρ = 0.90, p = 0.04). Our simulations provide a novel insight into the contributions of ASD to spatial and temporal heterogeneities of APDs, changes in excitation thresholds, and a potential explanation for wave fragmentation in the human atria due to sympathetic hyperactivity. Our work may aid in elucidating an electrophysiological link to arrhythmia initiation due to chronic stress among young patients.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".