Excessive Tumor Necrosis Factor Activation After Infarction Contributes to Susceptibility of Myocardial Rupture and Left Ventricular Dysfunction
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Bibliographic record
Abstract
BACKGROUND: We investigated the potential contributions of tumor necrosis factor-alpha (TNF-alpha) on the incidence of acute myocardial rupture and subsequent chronic cardiac dysfunction after myocardial infarction (MI) in TNF knockout (TNF-/-) mice compared with C57/BL wild-type (WT) mice. METHODS AND RESULTS: Animals were randomized to left anterior descending ligation or sham operation and killed on days 3, 7, 14, and 28. We monitored cardiac rupture rate, cardiac function, inflammatory response, collagen degradation, and net collagen formation. We found the following: (1) within 1 week after MI, 53.3% (n=120) of WT mice died of cardiac rupture, in contrast to 2.5% (n=80) of TNF-/- mice; (2) inflammatory cell infiltration and cytokine expression were significantly higher in the infarct zone in WT than TNF-/- mice on day 3; (3) matrix metalloproteinase-9 and -2 activity in the infarcted myocardium was significantly higher in WT than in TNF-/- mice on day 3; (4) on day 28 after MI compared with sham, there was a significant decrease in LV developed pressure (74%) and +/-dP/dt(max) (68.3%/65.3%) in WT mice but a less significant decrease in +/-dP/dt(max) (25.8%/28.8%) in TNF-/- mice; (5) cardiac collagen volume fraction was lower in WT than in TNF-/- mice on days 3 and 7 but higher on day 28 compared with TNF-/- mice; and (6) a reduction in myocyte apoptosis in TNF-/- mice occurred on day 28 compared with WT mice. CONCLUSIONS: Elevated local TNF-alpha in the infarcted myocardium contributes to acute myocardial rupture and chronic left ventricle dysfunction by inducing exuberant local inflammatory response, matrix and collagen degradation, increased matrix metalloproteinase activity, and apoptosis.
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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 | 0.000 | 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) | 0.000 | 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