Age-dependent response of the electrocardiogram to K<sup>+</sup>channel blockers in mice
Bibliographic record
Abstract
Developmental changes in electrocardiogram (ECG) and response to selective K(+) channel blockers were assessed in conscious, unsedated neonatal (days 1, 7, 14) and adult male mice (>60 days of age). Mean sinus R-R interval decreased from 120 +/- 3 ms in day 1 to 110 +/- 3 ms in day 7, 97 +/- 3 ms in day 14, and 81 +/- 1 ms in adult mice (P < 0.001 by ANOVA; all 3 groups different from day 1). In parallel, the mean P-R interval progressively decreased during development. Similarly, the mean Q-T interval decreased from 62 +/- 2 ms in day 1 to 50 +/- 2 ms in day 7, 47 +/- 8 ms in day 14 neonatal mice, and 46 +/- 2 ms in adult mice (P < 0.001 by ANOVA; all 3 groups are significantly different from day 1). Q-T(c) was calculated as Q- interval. Q-T(c) significantly shortened from 179 +/- 4 ms in day 1 to 149 +/- 5 ms in day 7 mice (P < 0.001). In addition, the J junction-S-T segment elevation observed in day 1 neonatal mice resolved by day 14. Dofetilide (0.5 mg/kg), the selective blocker of the rapid component of the delayed rectifier (I(Kr)) abolished S-T segment elevation and prolonged Q-T and Q-T(c) intervals in day 1 neonates but not in adult mice. In contrast, 4-aminopyridine (4-AP, 2.5 mg/kg) had no effect on day 1 neonates but in adults prolonged Q-T and Q-T(c) intervals and specifically decreased the amplitude of a transiently repolarizing wave, which appears as an r' wave at the end of the apparent QRS in adult mice. In conclusion, ECG intervals and configuration change during normal postnatal development in the mouse. K(+) channel blockers affect the mouse ECG differently depending on age. These data are consistent with the previous findings that the dofetilide-sensitive I(Kr) is dominant in day 1 mice, whereas 4-AP-sensitive currents, the transiently repolarizing K(+) current, and the rapidly activating, slowly inactivating K(+) current are the dominant K(+) currents in adult mice. This study provides background information useful for assessing abnormal development in transgenic mice.
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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 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".