Cardioprotective reperfusion strategies differentially affect mitochondria: Studies in an isolated rat heart model of donation after circulatory death (DCD).
- Sanz MN Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Farine E Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Niederberger P Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Méndez-Carmona N Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Wyss RK Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Arnold M Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Gulac P Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Fiedler GM Center of Laboratory Medicine, University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland.
- Gressette M UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
- Garnier A UMR-S 1180, INSERM, Université Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
- Carrel TP Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Tevaearai Stahel HT Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- Longnus SL Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
- 2018-07-19
Published in:
- American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - 2019
basic (laboratory) research/science
donors and donation: donation after circulatory death (DCD)
heart transplantation/cardiology
ischemia reperfusion injury (IRI)
metabolism/metabolite
Animals
Death
Heart Transplantation
Male
Mitochondria
Organ Preservation
Rats
Rats, Wistar
Reperfusion
Reperfusion Injury
Tissue Donors
Tissue and Organ Procurement
Warm Ischemia
English
Donation after circulatory death (DCD) holds great promise for improving cardiac graft availability; however, concerns persist regarding injury following warm ischemia, after donor circulatory arrest, and subsequent reperfusion. Application of preischemic treatments is limited for ethical reasons; thus, cardioprotective strategies applied at graft procurement (reperfusion) are of particular importance in optimizing graft quality. Given the key role of mitochondria in cardiac ischemia-reperfusion injury, we hypothesize that 3 reperfusion strategies-mild hypothermia, mechanical postconditioning, and hypoxia, when briefly applied at reperfusion onset-provoke mitochondrial changes that may underlie their cardioprotective effects. Using an isolated, working rat heart model of DCD, we demonstrate that all 3 strategies improve oxygen-consumption-cardiac-work coupling and increase tissue adenosine triphosphate content, in parallel with increased functional recovery. These reperfusion strategies, however, differentially affect mitochondria; mild hypothermia also increases phosphocreatine content, while mechanical postconditioning stimulates mitochondrial complex I activity and reduces cytochrome c release (marker of mitochondrial damage), whereas hypoxia upregulates the expression of peroxisome proliferator-activated receptor-gamma coactivator (regulator of mitochondrial biogenesis). Characterization of the role of mitochondria in cardioprotective reperfusion strategies should aid in the identification of new, mitochondrial-based therapeutic targets and the development of effective reperfusion strategies that could ultimately facilitate DCD heart transplantation.
- Language
-
- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1111/ajt.15024
- PMID 30019521
- Persistent URL
- https://folia.unifr.ch/global/documents/61154
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