Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration.

Wyss, Rahel Kathrin; Méndez Carmona, Natalia; Sanz-Garcia, Maria Nieves; Arnold, Maria Regula; Segiser, Adrian; Fiedler, Georg Martin; Carrel, Thierry; Djafarzadeh, Siamak; Tevaearai, Hendrik; Henning Longnus, Sarah (2019). Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death-consequences of ischemic duration. Journal of heart and lung transplantation, 38(6), pp. 647-657. Elsevier 10.1016/j.healun.2018.12.013

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Mitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death - consequences of ischemic duration.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

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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 content increased with ≥ 27 minutes of ischemia vs no ischemia (p < 0.05). Ischemia at ≥ 21 minutes decreased mitochondrial coupling, adenosine 5'-triphosphate content, mitochondrial Ca retention capacity, and increased oxidative damage vs no ischemia (p < 0.05). Reactive oxygen species (ROS) from reverse electron transfer increased with 21 and 27 minutes of ischemia vs no ischemia and 33 minutes of ischemia (p < 0.05), whereas ROS from forward electron transfer increased only with 33 minutes of ischemia vs no ischemia (p < 0.05). Mitochondrial coupling and adenosine 5'-triphosphate content correlated positively and cytochrome c, succinate, oxidative damage, and mitochondrial Ca content correlated negatively with cardiac functional recovery (p < 0.05). 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiovascular Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Herz- und Gefässchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Herz- und Gefässchirurgie

UniBE Contributor:

Wyss, Rahel Kathrin; Méndez Carmona, Natalia; Sanz-Garcia, Maria Nieves; Arnold, Maria Regula; Segiser, Adrian; Fiedler, Georg Martin; Carrel, Thierry; Djafarzadeh, Siamak; Tevaearai, Hendrik and Henning Longnus, Sarah

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1053-2498

Publisher:

Elsevier

Language:

English

Submitter:

Claudia Stalder

Date Deposited:

17 Jul 2019 15:01

Last Modified:

19 Jul 2019 17:12

Publisher DOI:

10.1016/j.healun.2018.12.013

PubMed ID:

30655178

Uncontrolled Keywords:

cardioprotection donation after circulatory death (DCD) functional recovery heart transplantation ischemia-reperfusion mitochondria reverse electron transfer

BORIS DOI:

10.7892/boris.127852

URI:

https://boris.unibe.ch/id/eprint/127852

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