Rate dependence of the effect of antiarrhythmic drugs delaying cardiac repolarization: an overview
Why this work is in the frame
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Bibliographic record
Abstract
Prolongation of the cardiac action potential and refractoriness (class III effect) is a potentially beneficial electrophysiological mechanism of action. However, this effect may be diminished or eliminated at rapid heart rates, so-called 'reverse rate dependence' of prolongation of repolarization. Action potential duration normally shortens as heart rate increases, due to increases in outward repolarizing currents, and/or decreases in inward depolarizing currents. The assessment of the effect of drugs on action potential duration is complicated by inter-species differences in ionic currents mediating repolarization, heterogeneity within the heart in repolarizing currents, and differential effect of drugs in different species, during differing experimental conditions, and at different rates of stimulation. In general, most drugs which predominantly block the IKr repolarizing current exhibit reverse rate-dependent effects on cardiac repolarization. Drugs or combinations of drugs which produce multiple ionic channel blocks and possibly those which block the IKs current, may be less prone to this potentially undesirable effect.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it