Myocardial and Skeletal Muscle Microvascular Dysfunction Manifests Prior to Diabetic Cardiomyopathy: Sex-Dependent Differences
Notice bibliographique
Résumé
Introduction: Microvascular dysfunction is a recognized sign of disease in heart failure progression. Blood vessels exhibit abnormal vasoreactivity in early stage, subsequently deteriorating to rarefaction and reduced perfusion. In managing heart failure patients, where diagnosis is typically possible only when the hypertrophic heart is irreversibly damaged, earlier diagnosis is key to improving management. In this study, we apply a blood-pool MRI method for assessing vasomodulation to investigate if it can sensitively detect abnormal leg muscle vasoreactivity posited to manifest before myocardial mvD. Methods: Male and female Sprague-Dawley rats were maintained on a high-fat, high-sugar diet or a control diet for 6 months after the induction of diabetes. Beginning at month 1 or 2 post-induction and every 2 months thereafter, rats underwent blood-pool MRI to assess vasoreactivity in the heart or skeletal muscle, respectively. Ablavar, a T1-reducing blood-pool contrast agent, was administered and the T1 relaxation time dynamically measured as animals breathed in mild CO2 levels to modulate vessels and elicit a vasodilatory response. CO2 levels were set at 5% for skeletal muscle and 10% for cardiac muscle, and the gas was administered for 10 minutes. At the final timepoint, invasive laser Doppler perfusion measurements in leg muscle were recorded to verify MRI results. Results/Discussion: In this study, we provide the first demonstration that both skeletal muscle and myocardial microvascular vasoreactivity is altered in a non-obese rodent model of type II diabetes, prior to the development of heart failure symptoms. In male rats, the normally unresponsive heart to 10% CO2 reveals a pro-vasoconstriction response beginning at 5 months post-diabetes. Abnormal leg skeletal muscle vasoreactivity appeared even earlier, at 2 months: the usual vasodilatory response to 5% CO2 is interrupted with periods of vasoconstriction in diseased rats. In female rats, differences were observed between healthy and diseased animals only within the first two months post-diabetes and not later. In the heart, vasodilation to 10% CO2 seen in healthy animals was abolished in diabetes. In skeletal muscle, 5% CO2 was suboptimal in inducing reproducible vasoreactivity, but young diabetic females responded by vasodilation only. Conclusion: Abnormal vasoreactivity presents earlier than overt structural and functional cardiac changes in both sexes in HFpEF and can be detected using blood-pool MRI in leg skeletal muscle before the myocardium. Our non-invasive MRI technology sets the foundation for a paradigm shift in diagnosing mvD during the early stages of HFpEF, opening the door for early intervention. This work was supported by the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation/Ontario Research Fund, Dean’s Spark Professorship, Medicine by Design Pivotal Experiment Fund [to H.L.M.C.]; Ted Rogers Centre for Heart Research PhD Education Fund, Scintica Instrumentation Inc [to S.L.]. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».