Abstract 19569: Inhibition of Cardiac Actin-Myosin Interaction by Blebbistatin Delays Onset of Ventricular Fibrillation during Myocardial Ischemia
Bibliographic record
Abstract
Sudden cardiac death in the context of coronary heart disease is most commonly the result of the occurrence of ventricular fibrillation (VF) following a new episode of myocardial ischemia. The electrophysiological disturbances that create a substrate for the development of VF in myocardial ischemia can be traced back to depletion of cellular ATP resulting from ATP consumption outstripping supply. Reducing cardiac ATP consumption may thus delay or inhibit the development of VF in ischemia. Therefore, we determined the effect of blebbistatin, a selective inhibitor of contraction that will reduce ATP consumption via reducing cardiac work, on the incidence and time of onset of ventricular fibrillation (VF) in an established model of regional myocardial ischemia. Isolated male rat hearts (n=12 per group) were randomized to one of 4 groups: control (vehicle 0.01% v/v), 0.1µM blebbistatin, 1µM blebbistatin, or 10µM blebbistatin. The ECG and left ventricular developed pressure (LVDP) were recorded in each heart. Hearts were perfused with test solution for 15 min, after which regional myocardial ischemia was induced by tightening a snare occluder placed around the left main coronary artery. Ischemia was maintained for 30 min. As expected, prior to myocardial ischemia, blebbistatin reduced LVDP (p>0.05 vs control), abolishing it at the 1µM and 10µM concentrations. Compared to control, the incidence of VF during ischemia was not affected at blebbistatin concentrations of 0.1µM and 1µM (83% and 92% respectively vs 83% in controls) and was reduced only as a trend with 10µM blebbistatin (67%; p<0.05). However, there was a concentration-dependent prolongation in the mean time to onset of VF with blebbistatin, which was significantly longer than the mean time to VF onset in controls at a concentration of 10µM (1367±113s vs 924±80s; p<0.05). This effect of blebbistatin was associated with a trend to increased ATP content in myocardial tissue samples taken from the ischemic zone as measured by luciferase luminescence assay. In conclusion, a reduction in cardiac work by inhibition of the cardiac contractile machinery can delay the onset of VF during myocardial ischemia, most likely as a consequence of delaying the depletion of myocardial ATP.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".