Duration of hypoxia in Sugen-Hypoxia model of severe pulmonary arterial hypertension does not affect the severity of pulmonary hypertension
Notice bibliographique
Résumé
Rationale: Pulmonary arterial hypertension (PAH) is a devastating pulmonary vascular disease characterized by pulmonary vascular rarefaction, elevated pulmonary vascular resistance and pressure, and right ventricular (RV) failure. While various models are used to study PAH, the SU5416-chronic hypoxia (SUHx) model is considered to be the gold-standard model. This model had always been theorized to be due to the two-hit nature of the model; however, it has never been optimized since discovery. Importantly, exposure to hypoxia requires specific animal hypoxia system and is a major limitation in experiment involving this model. Therefore, in this project, we assessed whether the length of hypoxia exposure affects the severity of the model. Methods: Fischer CDF rats were injected with SU5416 (20 mg/kg in DMSO, sc) and subjected to 3 weeks of hypoxia (10% O2) followed by 1 week of normoxia (SUHx-3 group, conventional model) or 2 weeks of hypoxia followed by 2 weeks of normoxia (SUHx-2 group, shortened Hx model). Echocardiography to assess cardiac structure and function, and RV systolic pressure (RVSP) measurements were performed for all rats at the 4-week time-point. Lung and heart samples from these rats were collected and histology analysis was performed to assess muscularization of pulmonary arteries and RV remodelling. Results: We observed similar increase in RVSP in SUHx-3 and SUHx-2 groups (108 mmHg and 102 mmHg, respectively) compared to controls (30 mmHg). Similarly, pulmonary artery acceleration time/pulmonary ejection time ratio was similarly reduced in SUHx-3 and SUHx-2 groups (0.212 and 0.165, respectively) compared to controls (0.33). No significant difference in RV structure was observed between SUHx-3 and SUHx-2 group as demonstrated by similar RV wall thickness (1.24 mm and 1.08 mm) and RV internal diameter (3.87 mm and 3.62 mm), Furthermore, RV functional parameters were also similar between SUHx-3 and SUHx-2 (Fractional shortening: 25.0% vs 24.9%; Tricuspid annular plane systolic excursion or TAPSE: 1.35 mm vs 1.32 mm; stroke volume index: 0.94 vs 0.92 mL/g). Conclusions: Duration of hypoxia exposure in SUHx model of severe PAH does not affect severity of pulmonary hypertension or RV remodelling. Canadian Institutes of Health Research, Canada Foundation for Innovation, Dalhousie University-Faculty of Medicine. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».