Cardioprotection in The Mouse Heart: Acute Protective Effects of An Estrogen Receptor Agonist
Notice bibliographique
Résumé
Background High calcium levels in ischemia promote contractile dysfunction and cell death in myocytes from aged or ovariectomized female mice. This suggests that low estrogen levels alter myocyte calcium homeostasis promoting ischemia and reperfusion (I/R) injury. Objective To determine whether the G‐protein coupled estrogen receptor (GPER) agonist, G1, enhances the benefits of a cardioplegic solution designed to protect hearts from ischemic damage. Methods Hearts were isolated from adult female and male mice (6–9 mos, n=28) for Langendorff perfusion experiments and then perfused with Krebs‐Henseleit buffer (37°C; 80 mmHg) for 15 min. Perfusion was interrupted and St. Thomas' 2 cardioplegic solution was delivered (6–9°C) either with G1 (500 nM), G1 (500 nM) + G15 (GPER antagonist; 1 μM) or with vehicle alone for 6 min. This was followed by 90 min global ischemia (23–24°C) and 30 min reperfusion (37°C). An enzyme‐linked immunosorbent assay (ELISA) was used to measure cardiac troponin‐I (cTnI) release from coronary effluent samples collected during reperfusion. Also, hearts were perfused with triphenyltetrazolium chloride (TTC) following reperfusion, which differentiated the infarcted (white) from viable (red) tissue. Results Post‐ischemic functional recovery in hearts perfused with cardioplegia + G1 (500 nM) was significantly better than cardioplegia alone in females. Left ventricular developed pressure (LVDP) recovered to 52.0 ± 11.5% for control vs. 75.6 ± 6.5% for G1 (p<0.05). Similar results were seen when the rates of pressure development (+dp/dt) and decay (−dp/dt) were assessed. Values for recovery of +dp/dt were 54.0 ± 12.1% vs. 77.6 ± 7.8% and for −dp/dt were 55.3 ± 12.2% vs. 81.0 ± 6.7% for control and G1, respectively. These effects of G1 were blocked by G15 (1 μM), where LVDP recovered to 57.0 ± 2%; +dp/dt and −dp/dt recovered to 60.4 ± 1.6% and 62.2 ± 3.6% respectively for G1 + G15 (p<0.05). cTnI release from female mouse hearts was slightly reduced in hearts treated with G1; values for cTnI were 9.0 ± 2.0 ng/ml and 6.5 ± 3.0 ng/ml for control and G1, respectively. Also, infarct sizes were smaller in the hearts treated with G1 (15.3 ± 3.6%) than the vehicle control (20.0 ± 3.5%), although this was not statistically significant. By contrast, no significant beneficial effects of G1 were observed in hearts from male mice (LVDP = 36.2 ± 5% for control vs. 49.0 ± 11.7% for G1). Conclusions These results demonstrate that addition of G1 enhances the cardioprotective properties of a standard cardioplegic solution and significantly improves functional recovery after ischemia in female mouse hearts. These results have the potential to improve outcomes during cardiac surgery. Support or Funding Information Canadian Institutes of Health research (CIHR), Nova Scotia Research and Innovation Graduate Scholarship (NSGS), Nova Scotia Health Research Foundation (NSHRF), Heart and Stroke Foundation (BrightRed Graduate Student Scholarship) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 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 | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 ».