• Maria N Sanz, Emilie Farine, Petra Niederberger, Natalia Méndez-Carmona, Rahel K Wyss, Maria Arnold, Patrik Gulac, Georg M Fiedler, Mélanie Gressette, Anne Garnier, Thierry P Carrel, Hendrik T Tevaearai Stahel, and Sarah L Longnus.
• Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
• Am. J. Transplant. 2019 Feb 1; 19 (2): 331-344.

AbstractDonation 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.© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

22 keywords...

hide…