Early and persistent activation of myocardial apoptosis, bax and caspases: insights into mechanisms of progression of heart failure
Bibliographic record
Abstract
The aim of this study was to test the hypothesis that persistent myocardial apoptosis contributes to progression of heart failure in a canine model of pacing-induced cardiomyopathy. Dogs were paced at 250 beats per minute for 1 week (n=9), 3 weeks (n=14) and 4 weeks (n=14) with normal dogs served as controls (n=12). Myocardial apoptosis was assessed by multiple methods including DNA fragmentation and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, bax and bcl-2 protein expression, and caspase activity. Pacing produced a progressive increase in left ventricular (LV) end diastolic pressure (LVEDP) and plasma norepinephrine levels with no significant increase in LV mass. The number of apoptotic cells was markedly increased after 1 week of pacing and remained increased at 4 weeks of pacing with characteristic DNA laddering. The increase in apoptosis was associated with bax protein expression and caspase activation while there was no detectable changes in bcl-2 protein expression. The estimated total number of apoptotic cells correlated with cardiac output and LVEDP (r=-0.69 and 0.59, respectively, P<0.001). Plasma norepinephrine and bax protein expression correlated significantly with the estimated total number of apoptotic myocytes (r=0.62 and 0.42, respectively, P<0.01). In conclusion, an early and persistent activation of myocardial apoptosis and pro-apoptotic factors is likely an important mechanism that contributes to the progression of heart failure in canine pacing-induced cardiomyopathy.
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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 | 0.001 | 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 | 0.001 |
| 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 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".