Abstract 562: Improvement In Left Ventricular Function Due To A Reduction Of Myocardial Fibrosis Following Myocardial Infarction Using A Purpose Designed Novel Anti Fibrotic Drug FT-011
Bibliographic record
Abstract
Introduction: Following myocardial infarction (MI), pathological deposition of excess collagen adversely effects cardiac function. We evaluated the role of a novel anti-fibrotic drug FT-011 (Fibrotech, Australia) in preventing fibrosis and preserving ventricular function. Methods : To first test for anti-fibrotic effects, isolated rat neonatal cardiac fibroblasts were stimulated with angiotensin II (AII)(0.1 μmol/L) or TGF-ß(10ng/ml) and treated with FT-011 (30–200 μmol/L) alone or in combination with the angiotensin II antagonist irbesartan (Irb)(10 −5 -10 −7 mmol/l). Effects on collagen synthesis were assessed by 3 H-proline incorporation. Subsequently, ten week old Sprague Dawley rats underwent LAD artery ligation to induce MI (or sham procedure), then treatment for 4 weeks with FT-011(200 mg/kg/d) or vehicle, starting 1 week post surgery. Left ventricular (LV) function was assessed by echocardiography (day 2 and 35 post-surgery) and cardiac catheterization (day 35). Total collagen (TC) deposition (by picrosirius red staining) and collagen subtypes I and III (C-I, C-III, by immunohistochemistry) were assessed. Results: A dose dependent reduction of collagen synthesis with FT-011 in response to both AII or TGF-ß stimulation (p<0.01), and a further reduction with FT-011±Irb was observed in vitro. In vivo, MIs were of comparable size. Treatment with FT-011 significantly reduced TC, C-I and C-III (p<0.05) in the myocardium, resulting in improved LV systolic function, normalization of diastolic function parameters (Table ) and improvement in heart failure with a reduction in lung/body weight ratio with FT-011 (p<0.05). Table: 35 day data [mean (SEM)]. Conclusion: Post MI treatment with FT-011 improved heart function by reducing pathological remodeling of the ventricle. This appears to be occurring at least in part via a direct anti-fibrotic effect of the drug.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".