Unusual Effects of a QT-Prolonging Drug, Arsenic Trioxide, on Cardiac Potassium Currents
Bibliographic record
Abstract
BACKGROUND: Cases of QT prolongation, torsades de pointes, and sudden death have been reported with arsenic trioxide (As2O3), a highly effective agent for acute promyelocytic leukemia. In this study, we evaluated the effects of As2O3 on repolarizing cardiac ion currents. METHODS AND RESULTS: In HERG- or KCNQ1+KCNE1-transfected CHO cells (n=32; total), As2O3 caused concentration-dependent block of both IKr and IKs, with an IC50 for tail current block of 0.14+/-0.01 micromol/L for IKr and 1.13+/-0.06 micromol/L for IKs. In contrast to other QT-prolonging drugs, As2O3 also activated a time-independent current that additional experiments identified as IK-ATP. CONCLUSIONS: As2O3 blocks both IKr and IKs at clinically relevant concentrations. On the other hand, it also activates IK-ATP, which maintains normal repolarization. We infer that variability in the extent of QT interval prolongation and onset of ventricular arrhythmias during arsenic therapy represents competing effects to block and activate multiple repolarizing potassium currents.
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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 | 0.000 |
| 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 | 0.000 | 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".