Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes
Why this work is in the frame
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Bibliographic record
Abstract
OBJECTIVES: Indirect evidence suggests a role for Ca(2+)-overload in electrical and mechanical alterations caused by atrial tachycardia. The present study assessed the alterations in cellular [Ca(2+)] and contractile function caused by rapid atrial cellular activation. METHODS: Intracellular Ca(2+) transients (CaT) and cell shortening (CS) were measured by microfluorometry (Indo-1 AM) and video edge-detection in isolated, field-stimulated canine atrial myocytes (37 degrees C). RESULTS: Abrupt increases in frequency (0.3-3 Hz) caused rapid increases in diastolic [Ca(2+)]i (DCa) that were maintained during rapid-pacing for up to 50 min. When short-term (3-min) rapid-pacing was imposed, CaT and CS increased initially upon returning to 0.3 Hz, but then declined rapidly to 64+/-5 and 49+/-7%, respectively, of pre-tachycardia values, returning to control after approximately 15 min. Post-tachycardia CaT and CS reductions were prevented by decreasing [Ca(2+)]o during tachycardia to prevent Ca(2+)-overload. CS reductions correlated with indices of Ca(2+) loading during tachycardia. Restoration of CaT to normal during post-tachycardia contractile dysfunction (by increasing [Ca(2+)]o) returned CS to normal, indicating that reduced Ca(2+) release, not reduced myofilament Ca(2+)-sensitivity, caused post-tachycardia contractile failure. Estimation of sarcoplasmic-reticulum Ca(2+)-stores (caffeine-induced Ca(2+)-release) confirmed tachycardia-induced Ca(2+)-loading and suggested that reduced Ca(2+)-stores decreased Ca(2+)-release post-tachycardia. CONCLUSIONS: Atrial tachycardia increases cellular Ca(2+)-loading, leading to post-tachycardia abnormalities in Ca(2+)-handling that produce contractile dysfunction. These findings are the first direct evidence for the frequently-postulated role of Ca(2+)-overload in tachycardia-induced abnormalities of atrial function.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 it