Efficacy of treprostinil in the SU5416‐hypoxia model of severe pulmonary arterial hypertension: haemodynamic benefits are not associated with improvements in arterial remodelling
Bibliographic record
Abstract
Background and Purpose Pulmonary arterial hypertension (PAH) is a life‐threatening disease that leads to progressive pulmonary hypertension, right heart failure and death. Parenteral prostaglandins (PGs), including treprostinil, a prostacyclin analogue, represent the most effective medical treatment for severe PAH. We investigated the effect of treprostinil on established severe PAH and underlying mechanisms using the rat SU5416 (SU, a VEGF receptor‐2 inhibitor)‐chronic hypoxia (Hx) model of PAH. Experimental Approach Male Sprague Dawley rats were injected with SU (20 mg·kg −1 , s.c.) followed by 3 weeks of Hx (10% O 2 ) to induce severe PAH. Four weeks post‐SU injection, baseline right ventricular (RV) systolic pressure (RVSP) was measured, and the rats were randomized to receive vehicle or treprostinil treatment (Trep‐100: 100 ng·kg −1 ·min −1 or Trep‐810: 810 ng·kg −1 ·min −1 ). Following 3 weeks of treatment, haemodynamic and echocardiographic assessments were performed, and tissue samples were collected for protein expression and histological analysis. Key Results At week 7, no difference in RVSP or RV hypertrophy was observed between vehicle and Trep‐100; however, Trep‐810 significantly reduced RVSP and RV hypertrophy. Trep‐810 treatment significantly improved cardiac structure and function. Further, a short‐term infusion of treprostinil in rats with established PAH at 4 weeks post‐SU produced an acute, dose‐dependent reduction in RVSP consistent with a vasodilator effect. However, chronic Trep‐810 treatment did not alter media wall thickness, degree of vascular occlusion or total vessel count in the lungs. Conclusions and Implications Treprostinil exerts therapeutic benefits in PAH through decreased vascular resistance and improved cardiac structure and function; however, treprostinil treatment does not have direct impact vascular remodelling.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".