Mechano-arrhythmogenicity is enhanced during late repolarisation in ischemia and driven by a TRPA1-, calcium-, and reactive oxygen species-dependent mechanism
Bibliographic record
Abstract
ABSTRACT Background Cardiac dyskinesis in regional ischemia results in arrhythmias through mechanically-induced changes in electrophysiology (‘mechano-arrhythmogenicity’) that involve ischemic alterations in voltage-calcium (Ca 2+ ) dynamics, creating a vulnerable period (VP) in late repolarisation. Objective To determine cellular mechanisms of mechano-arrhythmogenicity in ischemia and define the importance of the VP. Methods and Results Voltage-Ca 2+ dynamics were simultaneously monitored in rabbit ventricular myocytes by dual-fluorescence imaging to assess the VP in control and simulated ischemia (SI). The VP was longer in SI than in control (146±7 vs 54±8ms; p <0.0001) and was reduced by blocking K ATP channels with glibenclamide (109±6ms; p <0.0001). Cells were rapidly stretched (10-18% increase in sarcomere length over 110-170ms) with carbon fibres during diastole or the VP. Mechano-arrhythmogenicity, associated with stretch and release in the VP, was greater in SI than control (7 vs 1% of stretches induced arrhythmias; p <0.005) but was similar in diastole. Arrhythmias during the VP were more complex than in diastole (100 vs 69% had sustained activity; p <0.05). In the VP, incidence was reduced with glibenclamide (2%; p <0.05), by chelating intracellular Ca 2+ (BAPTA; 2%; p <0.05), blocking mechano-sensitive TRPA1 (HC-030031; 1%; p <0.005), or by scavenging (NAC; 1%; p <0.005) or blocking reactive oxygen species (ROS) production (DPI; 2%; p <0.05). Ratiometric Ca 2+ imaging revealed that SI increased diastolic Ca 2± (+9±1%, p <0.0001), which was not prevented by HC-030031 or NAC. Conclusion In ischemia, mechano-arrhythmogenicity is enhanced specifically during the VP and is mediated by ROS, TRPA1, and Ca 2+ .
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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".