Left ventricular contractile function is critically dependent on descending sympathetic control and can be restored with minocycline after spinal cord injury
Notice bibliographique
Résumé
OBJECTIVE We and others have shown that individuals with spinal cord injury (SCI) have significantly impaired cardiac function, which likely explains this population's increased odds of developing heart disease. We recently determined that pressure and volume generating capacity are both reduced following SCI and that only volumetric indices could be restored with passive rehabilitation (i.e. passive hind‐limb cycling). Conversely, we were able to partially restore pressure generating capacity using Dobutamine, directly showing that sympathetic input to the heart is critical for the maintenance of left ventricular pressure generating capacity. To this end, we sought to determine if minocycline, which has previously been shown to preserve descending supraspinal motor connections after SCI, could restore pressure generating capacity of the heart after severe spinal cord contusion in the rodent. DESIGN/METHOD Male Wistar rats (n=11) underwent T3 contusion SCI and were randomly stratified into either a treated (minocycline; n=5) or vehicle control (n=6). Minocycline was given intraperitoneally at one‐hour post injury (90mg/kg) and then every 12 hours for 14 days (45mg/kg). At two months post injury animals were anesthetized with urethane and ventilated via tracheotomy. A left ventricular pressure volume catheter was inserted via a right carotid, closed chest approach and placed into the left ventricle under pressure guidance. Basal left ventricular function was immediately assessed, followed by preload manipulation and subsequent determination of load‐independent (i.e. Ees, PRSW, dPdt max ‐EDV) function using inferior vena cava occlusions. Between group differences in load‐dependent and load‐independent function were assessed using independent samples t‐tests with significance offset at p<0.05. RESULTS Animals treated with minocycline showed significantly higher max systolic pressure (p=0.008; ) and dPdt max (p=0.040) compared to vehicle. No differences in heart rate were observed between groups. Load‐independent left ventricular function was significantly higher with treatment of minocycline compared to vehicle (Ees: 1.36 ± 0.46 vs. 0.72 ± 0.35; p=0.028; dPdt max ‐EDV: 102.4 ± 16.4 vs. 41.6 ± 18.4; p<0.001). CONCLUSIONS Minocycline is currently in Phase III clinical trial for the improvement of motor function after SCI. Our data provide clear evidence that minocycline is able to improve load dependent and independent left ventricular function after SCI, likely due to increased sparing of descending sympatho‐excitatory pathways to the heart and adrenal medulla. Collectively, these results demonstrate a clear line of treatment that is able to restore pressure generating capacity of the left ventricle in this population. Support or Funding Information JW Squair is supported by: Frederick Banting and Charles Best Canada Graduate Scholarship, MD/PhD Studentship from the Canadian Institutes of Health Research, Killam Doctoral Scholarship and Four Year Fellowship from the University of British Columbia. This work was principally supported by the Heart and Stroke Foundation of Canada (CR West) and a seed grant from the International Collaboration on Repair Discoveries (AV Krassioukov).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 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) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».