Passive hind‐limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury
Notice bibliographique
Résumé
Key points Using a wide array of experimental approaches, we demonstrate for the first time that spinal cord injury is associated with a rapid and sustained impairment in cardiac structure and function that is present as early as 1 week post‐injury. We provide novel data demonstrating that spinal cord injury elicits an altered Starling curve and myocardial fibrosis. The latter of these may be secondary to an up‐regulation of transforming growth factor beta‐1 and mothers against decapentaplegic homolog 3 mRNA, both of which form part of a well‐known fibrotic signalling pathway. Passive hind‐limb cycling averts the spinal cord injury‐induced impairments in cardiac structure and function, prevents myocardial fibrosis and improves blood lipid profiles. Passive lower‐limb cycling represents an elegant, cost‐effective and widely accessible therapeutic strategy that may reduce the clinical cardiovascular burden imposed by spinal cord injury and other neurological disorders. Abstract Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio‐metabolic responses to SCI and to establish whether passive hind‐limb cycling elicits a cardio‐protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind‐limb cycling (SCI‐EX; 2 × 30 min day −1 , 5 days week −1 for 4 weeks beginning 6 days post‐SCI). On day 32, cardio‐metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats ( n = 6 SCI and n = 6 SCI‐EX) underwent in vivo echocardiography and basal haemodynamic assessments pre‐SCI and at days 7, 14 and 32 post‐SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up‐regulation of transforming growth factor beta‐1 (TGFβ 1 ) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI‐EX, the initial reduction in left ventricular dimensions and function at day 7 post‐SCI was completely reversed by day 32 post‐SCI, and there were no differences in myocardial contractility between SCI‐EX and CON. Collagen deposition was similar between SCI‐EX and CON. TGFβ 1 and Smad3 were down‐regulated in SCI‐EX. Blood lipid profiles were improved in SCI‐EX versus SCI. We provide compelling novel evidence that passive hind‐limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.
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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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 | 0,001 |
| 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 ».