| Autor: |
Daniel Scheiber, Elric Zweck, Sophie Albermann, Tomas Jelenik, Maximilian Spieker, Florian Bönner, Patrick Horn, Heinz‐Peter Schultheiss, Ganna Aleshcheva, Felicitas Escher, Udo Boeken, Payam Akhyari, Michael Roden, Malte Kelm, Julia Szendroedi, Ralf Westenfeld |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
ESC Heart Failure, Vol 8, Iss 6, Pp 4674-4684 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2055-5822 |
| DOI: |
10.1002/ehf2.13607 |
| Popis: |
Abstract Aims Acute cellular rejection (ACR) following heart transplantation (HTX) is associated with long‐term graft loss and increased mortality. Disturbed mitochondrial bioenergetics have been identified as pathophysiological drivers in heart failure, but their role in ACR remains unclear. We aimed to prove functional disturbances of myocardial bioenergetics in human heart transplant recipients with mild ACR by assessing myocardial mitochondrial respiration using high‐resolution respirometry, digital image analysis of myocardial inflammatory cell infiltration, and clinical assessment of HTX patients. We hypothesized that (i) mild ACR is associated with impaired myocardial mitochondrial respiration and (ii) myocardial inflammation, systemic oxidative stress, and myocardial oedema relate to impaired mitochondrial respiration and myocardial dysfunction. Methods and results We classified 35 HTX recipients undergoing endomyocardial biopsy according International Society for Heart and Lung Transplantation criteria to have no (0R) or mild (1R) ACR. Additionally, we quantified immune cell infiltration by immunohistochemistry and digital image analysis. We analysed mitochondrial substrate utilization in myocardial fibres by high‐resolution respirometry and performed cardiovascular magnetic resonance (CMR). ACR (1R) was diagnosed in 12 patients (34%), while the remaining 23 patients revealed no signs of ACR (0R). Underlying cardiomyopathies (dilated cardiomyopathy 50% vs. 65%; P = 0.77), comorbidities (type 2 diabetes mellitus: 50% vs. 35%, P = 0.57; chronic kidney disease stage 5: 8% vs. 9%, P > 0.99; arterial hypertension: 59% vs. 30%, P = 0.35), medications (tacrolimus: 100% vs. 91%, P = 0.54; mycophenolate mofetil: 92% vs. 91%, P > 0.99; prednisolone: 92% vs. 96%, P > 0.99) and time post‐transplantation (21.5 ± 26.0 months vs. 29.4 ± 26.4 months, P = 0.40) were similar between groups. Mitochondrial respiration was reduced by 40% in ACR (1R) compared with ACR (0R) (77.8 ± 23.0 vs. 128.0 ± 33.0; P 14 CD3+‐lymphocytes/mm2 (100% sensitivity, 82% specificity; P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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