Abstract 12654: PBI-4050 Therapy Selectively Improves Pulmonary Hypertension, Lung Remodeling and Right Ventricular Function in Heart Failure With Reduced Ejection Fraction
Bibliographic record
Abstract
Introduction: There is currently no approved treatment for the most prevalent form of PH that is associated with left heart disease (Group II PH). Heart failure with reduced ejection fraction (HFrEF) causes lung remodeling characterized by myofibroblasts proliferation and fibrosis leading to a restrictive lung syndrome contributing to PH and RV dysfunction. Hypothesis: We evaluated PBI-4050, a novel first-in-class agent with anti-fibrotic and anti-proliferative actions, for the treatment of PH in a model of HFrEF. Methods: HFrEF was induced by myocardial infarction (MI) after coronary artery ligation in rats. Two weeks after surgery, sham-operated and MI groups were treated with PBI-4050 (200 mg/kg/day by gavage) or with saline for 3 weeks. Animals were analyzed according to pathological infarct size into large MI (≥35% LV) and small to medium MI (< 35%). Hemodynamic evaluation was performed with microtip cathethers and lung function testing evaluated with a Flexivent respirator. Cardiac ultrasound was performed at 2 weeks and at 5 weeks. Scar size and lung fibrosis were quantified by histology. Results: Pathological infarct size correlated with echocardiographic wall motion score index (r 2 =0.73, p<0.001). Large MI (≥35% LV) resulted in PH and RVH with a restrictive lung syndrome. For a similar infarct size, PBI-4050 did not affect LV function but markedly reduced PH and RVH. The compensatory increase in RV contractility was normalized by PBI-4050. PBI-4050 reduced lung remodeling evidenced by a reduction in lung weight and improved respiratory compliance. Finally, lung fibrosis was reduced by PBI-4050 with histological evidence of reduced alveolar wall cellular proliferation. Conclusions: PBI-4050 effectively reduces PH and RVH in HFrEF by reducing lung fibrosis and remodeling. This novel agent decreases the associated restrictive lung syndrome and recovers RV function without affecting LV function. PBI-4050 is a promising therapy for group II PH.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".