التفاصيل البيبلوغرافية
| العنوان: |
Beneficial Effects of Tacrolimus on Brain-Death-Associated Right Ventricular Dysfunction in Pigs |
| المؤلفون: |
Asmae Belhaj, Laurence Dewachter, Astrid Monier, Gregory Vegh, Sandrine Rorive, Myriam Remmelink, Mélanie Closset, Christian Melot, Jacques Creteur, Isabelle Salmon, Benoît Rondelet |
| المصدر: |
International Journal of Molecular Sciences; Volume 24; Issue 13; Pages: 10439 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2023 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
heart transplantation, right ventricular dysfunction, brain death, FK506, tacrolimus, calcineurin inhibitor, inflammation, apoptosis |
| جغرافية الموضوع: |
agris |
| الوصف: |
Background: Right ventricular (RV) dysfunction remains a major problem after heart transplantation and may be associated with brain death (BD) in a donor. A calcineurin inhibitor tacrolimus was recently found to have beneficial effects on heart function. Here, we examined whether tacrolimus might prevent BD-induced RV dysfunction and the associated pathobiological changes. Methods: After randomized tacrolimus (n = 8; 0.05 mg·kg−1·day−1) or placebo (n = 9) pretreatment, pigs were assigned to a BD procedure and hemodynamically investigated 1, 3, 5, and 7 h after the Cushing reflex. After euthanasia, myocardial tissue was sampled for pathobiological evaluation. Seven pigs were used as controls. Results: Calcineurin inhibition prevented increases in pulmonary vascular resistance and RV-arterial decoupling induced by BD. BD was associated with an increased RV pro-apoptotic Bax-to-Bcl2 ratio and RV and LV apoptotic rates, which were prevented by tacrolimus. BD induced increased expression of the pro-inflammatory IL-6-to-IL-10 ratio, their related receptors, and vascular cell adhesion molecule-1 in both the RV and LV. These changes were prevented by tacrolimus. RV and LV neutrophil infiltration induced by BD was partly prevented by tacrolimus. BD was associated with decreased RV expression of the β-1 adrenergic receptor and sarcomere (myosin heavy chain [MYH]7-to-MYH6 ratio) components, while β-3 adrenergic receptor, nitric oxide-synthase 3, and glucose transporter 1 expression increased. These changes were prevented by tacrolimus. Conclusions: Brain death was associated with isolated RV dysfunction. Tacrolimus prevented RV dysfunction induced by BD through the inhibition of apoptosis and inflammation activation. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Molecular Immunology; https://dx.doi.org/10.3390/ijms241310439Test |
| DOI: |
10.3390/ijms241310439 |
| الإتاحة: |
https://doi.org/10.3390/ijms241310439Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.F3452 |
| قاعدة البيانات: |
BASE |
