Combination <i>I</i><sub>K1</sub> and <i>I</i><sub>Kr</sub> channel blockade: no additive lowering of the defibrillation threshold
Bibliographic record
Abstract
Selective blockade of the inward rectifier potassium channel I(K1) by barium, or of the rapidly activating delayed rectifier potassium channel I(Kr) by D,L-sotalol, prolongs repolarization and reduces the defibrillation threshold (DFT). This study hypothesized that combination I(K1) and I(Kr) channel block would produce concentration-dependent additive effects on DFT and ventricular refractoriness. A range of barium and D,L-sotalol concentrations, alone and in combination, were examined with respect to DFT, ventricular effective refractory period (VERP), and ventricular fibrillation cycle length (VFCL) in 133 Langendorff-perfused rabbit hearts. Barium produced a concentration-dependent reduction of DFT (-49+/-4%), with concentration-dependent increases in VERP (26+/-6%) and VFCL (42+/-18%). D,L-Sotalol produced a concentration-dependent lowering of DFT (-53+/-6%) with a concentration-dependent increase in VFCL (34+/-8%) but not VERP. Low (1.6 microM), intermediate (3.1 microM), and high (12.5 microM) barium concentrations combined with varying D,L-sotalol concentrations produced equal or smaller decreases in DFT compared with corresponding doses of barium or D,L-sotalol alone. Except at the lowest concentrations of barium (1.6 and 3.1 microM) (p < 0.05), there was no significant additive interaction between barium and D,L-sotalol on VERP or VFCL. Combination I(K1) and I(Kr) channel block by barium and D,L-sotalol does not produce additive reduction of DFT.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".