The class III antiarrhythmic drugs dofetilide and sotalol prevent AF induction by atrial premature complexes at doses that fail to terminate AF
Bibliographic record
Abstract
BACKGROUND: Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS: We applied 240-electrode epicardial mapping and programmed stimulation in a vagotonic dog model of AF before and after dofetilide or sotalol. RESULTS: Under control conditions, sustained AF could be induced by single S(2) extrastimuli that caused unidirectional block and macroreentry. Sotalol (2 mg/kg) and dofetilide (0.04 mg/kg) failed to terminate AF in any dog, but prevented AF induction by S(2) stimuli in 19/22 (86%) and 4/5 (80%) of animals, respectively. With sotalol and dofetilide, unidirectional block still occurred, but wavefront reentry failed. The prevention of S(2)-induced reentry was related to large increases in the effective refractory period (ERP) at a BCL of 1000 ms, leading to ERPs that exceeded the conduction delay following S(2). Reverse use-dependent effects resulted in smaller ERP increases at BCLs closer to the AF cycle length. Although the number of zones of reactivation per cycle during sustained AF were decreased by sotalol and dofetilide, the changes were small and insufficient to terminate AF. CONCLUSIONS: Sotalol and dofetilide prevent AF initiation by premature depolarizations at doses that fail to terminate vagotonic AF, by increasing ERP at the basic cycle length beyond the associated conduction delay that leads to reentry.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".