Adverse structural and mechanical remodelling of main pulmonary artery in experimental pulmonary arterial hypertension is associated with impaired right ventricle-pulmonary artery coupling and function
Bibliographic record
Abstract
Abstract Rationale Coupling between right ventricular function and the pulmonary vasculature determines outcomes in pulmonary arterial hypertension. The mechanics of the main pulmonary artery is an important but understudied determinant of right ventricular-pulmonary artery coupling. Objectives To investigate the histology and mechanics of the pulmonary artery in relationship to right ventricular remodeling, mechanics, hemodynamics and coupling in experimental pulmonary arterial hypertension. Methods In a sugen+hypoxia rat model of pulmonary arterial hypertension, right ventricular hemodynamics were assessed by conductance catheters. Active tension-strain curves were generated using echocardiography. Main pulmonary artery and right ventricle free-wall were harvested to determine their macro- and micro-structure, composition, and mechanical properties. Comprehensive multivariate analyses elucidated relationships between pulmonary artery and right ventricle mechanics, structure and coupling. Measurements and Main Results Pulmonary hypertensive main pulmonary arteries developed fibrosis relative to healthy controls, as did right ventricles, which also hypertrophied, with re-orientation of muscle fibres toward a tri-layer architecture reminiscent of normal left ventricular architecture. Increased glycosaminoglycan deposition and increased collagen-to-elastin ratio in the pulmonary artery; and increased collagen, as well as hypertrophy and reorganization of myofibers in the right ventricle, led to increased stiffness. This increase in stiffness was more pronounced in the longitudinal direction in the high- and low-strain regime for the pulmonary artery and right ventricle, respectively, causing increased mechanical anisotropy. Main pulmonary artery stiffening correlated significantly with right ventricular tissue mechanical remodelling and reduced systolic performance, cardiac output and right ventricle-pulmonary artery coupling. Conclusions Compositional, structural, and mechanical changes in the main pulmonary artery correlate with adverse right ventricular remodeling, mechanics, function and coupling in pulmonary arterial hypertension. Therefore, increasing mechanical compliance of the large pulmonary arteries may be an important and novel therapeutic strategy for mitigating right ventricular failure.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".