LAUSR

Purpose Hearts donated from cardiac death donors (DCD) can be successfully maintained by ex-vivo machine perfusion (EVMP) with blood. Donor heart function will be deteriorated depending on the warm ischemia time (WIT). However, the reconditioning capability of machine perfusion with a novel crystalloid preservation solution histidine-tryptophane-ketoglutarate-N (HTK-N) has not been investigated. Methods In a pig model of DCD, cardiac death was induced by termination of ventilation, followed by harvesting of donor hearts. After a total WIT of 30 min, hearts underwent either 4 h of EVMP with warm donor blood (DCD-B) in a beating state or cold EVMP with oxygenated HTK-N (DCD-HTK-N), both followed by reperfusion in Langendorff fashion, or were directly undertaken reperfusion (DCD) (N=8/group). During reperfusion, hemodynamic function was measured by a left ventricular (LV) balloon catheter. Oxidative and nitrosative stress as well as necrosis pathways and morphology of LV-tissue samples were analyzed by 4-hydroxy-2-nonenal (HNE), nitrotyrosine (NT), poly(adenosine diphosphate-ribose)polymerase (PARP) and hematoxylin-eosin (HE) staining. Results After 60 min of reperfusion, DCD-HTK-N hearts showed significantly improved end-systolic pressure (ESP = 172±10 mmHg, p=0.02) and rate of pressure increasement (dp/dtmax = 2161±214 mmHg/s, p=0.005) compared to immediately reperfused DCD-hearts (ESP = 132±5 mmHg, dp/dtmax = 1240±167 mmHg/s) at 20 mL of balloon volume. dp/dtmax and rate of pressure decreasement (dp/dtmin = -1501±228, p=0.005) were also significantly improved after EVMP with HTK-N compared to blood perfusion (dp/dtmax = 1177±156, dp/dtmin = - 637±79). After HTK-N perfusion, oxidative and nitrosative stress as well as necrosis were significantly decreased compared to direct reperfusion (HNE: p=0.005, NT: p=0.002, PARP: p=0.019) or blood perfusion (HNE: p Conclusion EVMP with HTK-N is able to recondition systolic function of DCD-hearts and leads to improved diastolic donor heart function compared to EVMP with blood by reducing oxidative stress, nitrosative stress as well as preventing cardiomyocytes from morphologic change.