Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by reducing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff-perfused mouse hearts
Bibliographic record
Abstract
In the current study, arrhythmogenic effects of the gap junction inhibitor heptanol (0.05 mM) were examined in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricular epicardium during right ventricular pacing. Regular activity was observed both prior and subsequent to application of heptanol in all of the 12 hearts studied during 8 Hz pacing. By contrast, induced ventricular tachycardia (VT) was observed after heptanol treatment in 6/12 hearts using a S1S2 protocol (Fisher's exact test; P<0.05). The arrhythmogenic effects of heptanol were associated with increased activation latencies from 13.2±0.6 to 19.4±1.3 msec (analysis of variance; P<0.001) and reduced conduction velocities (CVs) from 0.23±0.01 to 0.16±0.01 msec (analysis of variance; P<0.001) in an absence of alterations in action potential durations (ADPs) at x=90% (38.0±1.0 vs. 38.3±1.8 msec), 70% (16.8±1.0 vs. 19.5±0.9 msec), 50% (9.2±0.8 vs. 10.1±0.6 msec) or 30% (4.8±0.5 vs. 6.3±0.6 msec) repolarization (APDx) or in effective refractory period (ERPs) (39.6±1.9 vs. 40.6±3.0 msec) (all P>0.05). Consequently, excitation wavelengths (λ; CV x ERP) were reduced from 9.1±0.6 to 6.5±0.6 mm (P<0.01), however critical intervals for re‑excitation (APD90 ‑ ERP) were unaltered (‑1.1±2.4 vs. ‑2.3±1.8 msec; P>0.05). Together, these observations demonstrate for the first time, to the best of our knowledge, that inhibition of gap junctions alone using a low heptanol concentration (0.05 mM) was able to reduce CV, which alone was sufficient to permit the induction of VT using premature stimulation by reducing λ, which therefore appears central in the determination of arrhythmic tendency.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 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".