Novel Model of Constrictive Pericarditis Associated With Autoimmune Heart Disease in Interferon-γ–Knockout Mice
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: Constrictive pericarditis represents a serious hemodynamic syndrome that may lead to heart failure. Studies of its pathophysiological mechanisms have been impeded by the lack of an animal model. METHODS AND RESULTS: Cardiac myosin-induced experimental autoimmune myocarditis in interferon (IFN)-gamma-knockout (KO) mice results in increased cardiac inflammation and development of severe grossly detectable pericarditis. Using in vivo pressure-volume studies, we found that the acute phase of experimental autoimmune myocarditis in IFN-gamma-KO mice was characterized by reduced left ventricular (LV) volumes compared with wild-type mice. The KO mice exhibited a classic restrictive/constrictive phenotype with decreased cardiac output, increased chamber stiffness, preserved ejection fraction, and impaired diastolic filling, characterized by reduced deceleration time and pressure tracings showing the square root sign similar to that observed in clinical cases of constrictive pericarditis. This phenotype was not associated with the severity of myocarditis but correlated with the presence of grossly detectable adhesive pericarditis present only in the KO group and characterized by increased pericardial inflammation and fibrosis. Comparison of IFN-gamma-KO and wild-type mice matched for the severity of myocardial disease further confirmed that pericarditis, and not myocarditis, was responsible for smaller LV volumes, reduced cardiac output, increased cardiac stiffness, and increased peak filling rate adjusted for end-diastolic volumes in KO mice. CONCLUSIONS: Autoimmune heart disease in IFN-gamma-KO mice results in increased pericardial inflammation and fibrosis, leading to constrictive phenotype during the acute phase of disease. It represents a novel animal model of constrictive pericarditis.
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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