Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration.
cardioprotection
functional recovery;reverse electron transfer
heart transplantation;donation after circulatory death (DCD)
ischemia-reperfusion
mitochondria
Journal
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117
Titre abrégé: J Heart Lung Transplant
Pays: United States
ID NLM: 9102703
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
27
08
2018
revised:
13
11
2018
accepted:
18
12
2018
pubmed:
19
1
2019
medline:
21
10
2020
entrez:
19
1
2019
Statut:
ppublish
Résumé
Cardioprotection and graft evaluation after ischemia-reperfusion (IR) are essential in facilitating heart transplantation with donation after circulatory death. Given the key role of mitochondria in IR, we aimed to investigate the tolerance of cardiac mitochondria to warm, global ischemia and to determine the predictive value of early reperfusion mitochondria-related parameters for post-ischemic cardiac recovery. Isolated, working rat hearts underwent 0, 21, 24, 27, 30, or 33 minutes of warm, global ischemia, followed by 60 minutes of reperfusion. Functional recovery (developed pressure × heart rate) was determined at 60 minutes of reperfusion, whereas mitochondrial integrity was measured at 10 minutes of reperfusion. Functional recovery at 60 minutes of reperfusion decreased with ≥ 27 minutes of ischemia vs no ischemia (n = 7-8/group; p < 0.01). Cytochrome c, succinate release, and mitochondrial Ca Mitochondrial dysfunction occurs with shorter periods of ischemia than cardiac dysfunction. Mitochondrial coupling, ROS emission from reverse electron transfer, and calcium retention are particularly sensitive to early reperfusion injury, reflecting potential targets for cardioprotection. Indicators of mitochondrial integrity may be of aid in evaluating suitability of donation after circulatory death grafts for transplantation.
Sections du résumé
BACKGROUND
Cardioprotection and graft evaluation after ischemia-reperfusion (IR) are essential in facilitating heart transplantation with donation after circulatory death. Given the key role of mitochondria in IR, we aimed to investigate the tolerance of cardiac mitochondria to warm, global ischemia and to determine the predictive value of early reperfusion mitochondria-related parameters for post-ischemic cardiac recovery.
METHODS
Isolated, working rat hearts underwent 0, 21, 24, 27, 30, or 33 minutes of warm, global ischemia, followed by 60 minutes of reperfusion. Functional recovery (developed pressure × heart rate) was determined at 60 minutes of reperfusion, whereas mitochondrial integrity was measured at 10 minutes of reperfusion.
RESULTS
Functional recovery at 60 minutes of reperfusion decreased with ≥ 27 minutes of ischemia vs no ischemia (n = 7-8/group; p < 0.01). Cytochrome c, succinate release, and mitochondrial Ca
CONCLUSIONS
Mitochondrial dysfunction occurs with shorter periods of ischemia than cardiac dysfunction. Mitochondrial coupling, ROS emission from reverse electron transfer, and calcium retention are particularly sensitive to early reperfusion injury, reflecting potential targets for cardioprotection. Indicators of mitochondrial integrity may be of aid in evaluating suitability of donation after circulatory death grafts for transplantation.
Identifiants
pubmed: 30655178
pii: S1053-2498(18)31790-X
doi: 10.1016/j.healun.2018.12.013
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
647-657Informations de copyright
Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.