Abstract 363: Dantrolene Decreases Susceptibility to Refibrillations by Restoring Vf Dependent Cardiac Calcium Handling Dysfunction
Bibliographic record
Abstract
Background: Ventricular refibrillation frequently occurs after successful defibrillation of Ventricular Fibrillation (VF) and negatively affects outcomes. Diastolic elevation in cytosolic calcium and dysfunction in calcium handling is proposed to underlie post-shock arrhythmias. Ryanodine Receptor 2 (RyR2) is the major calcium handling protein in cardiomyocytes. its dysfunction causes diastolic calcium leak from sarcoplasmic reticulum and calcium transient amplitude alternans (Ca-Alt), which can lead to arrhythmias. We hypothesized Dantrolene protects against refibrillations by restoring cardiac calcium handling and stabilizing RyR2 after VF. Methods and Results: Hearts from 14 healthy New-Zealand rabbits were excised and perfused using Langendorff method; VF(+ISO) was induced by burst pacing and left untreated for 4 min. Hearts received either Dantrolene (20μM) or saline during VF. Upon defibrillation, 4 more VF episodes were attempted. Sustainability (VF≥60 sec) and inducibility of refibrillations (VF≥10 sec) was evaluated. Calcium mapping using RhoD-2 was performed to assess Ca-Alt and diastolic Spontaneous Calcium Elevation (SCaE). Ca-Alt was defined as ≥10% variability in Calcium transient amplitudes. SCaE amplitude was measured during diastolic pause after termination of pacing. In total, 83.33% of attempts to induce refibrillation in controls were successful compared to 41.18% in Dantrolene-treated hearts. (P=0.007) Dantrolene (20μM) significantly decreased SCaE amplitude post VF. (Table 1) Ca-Alt emerged at shorter PCL in Dantrolene-treated hearts with 10% decrease from 195±9.5ms at baseline to 173±6.7ms post-VF compared to 11% increase in controls from 215±20ms to 235±8ms. (P=0.05) Conclusion: Dantrolene ameliorated arrhythmogenic diastolic SCaE caused by VF and increased calcium alternans threshold and may be the basis for the decreased susceptibility of treated hearts to refibrillations.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".