ORIGINAL PRE-CLINICAL SCIENCE A whole blood–based perfusate provides superior preservation of myocardial function during ex vivo heart perfusion Christopher W. White, MD, a,b Devin Hasanally, BS, b Paul Mundt, BS, a Yun Li, MD, b Bo Xiang, DMD, c Julianne Klein, MD, d Alison Müller, MS, b Emma Ambrose, BS, b Amir Ravandi, MD, PhD, a,b Rakesh C. Arora, MD, PhD, a,b Trevor W. Lee, MD, e Larry V. Hryshko, PhD, b Stephen Large, MD, f Ganghong Tian, MD, PhD, c and Darren H. Freed, MD, PhD a,b,g,h From the a Cardiac Sciences Program, University of Manitoba; b Institute of Cardiovascular Sciences, St. Boniface Hospital; c National Research Council Institute for Biodiagnostics; Departments of d Pathology; and e Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; f Papworth Hospital, Cambridge, United Kingdom; g Cardiac Surgery, Mazankowski Alberta Heart Institute; and the h Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada. KEYWORDS: ex vivo heart perfusion; myocardial function; oxygen delivery; myocardial energy metabolism; hemoglobin-based oxygen carrier; HBOC; ex vivo perfusate BACKGROUND: Ex vivo heart perfusion (EVHP) provides the opportunity to resuscitate unused donor organs and facilitates assessments of myocardial function that are required to demonstrate organ viability before transplantation. We sought to evaluate the effect of different oxygen carriers on the preservation of myocardial function during EVHP. METHODS: Twenty-seven pig hearts were perfused ex vivo in a normothermic beating state for 6 hours and transitioned into working mode for assessments after 1 (T1), 3 (T3), and 5 (T5) hours. Hearts were allocated to 4 groups according to the perfusate composition. Red blood cell concentrate (RBC, n ¼ 6), whole blood (RBCþPlasma, n ¼ 6), an acellular hemoglobin-based oxygen carrier (HBOC, n ¼ 8), or HBOC plus plasma (HBOCþPlasma, n ¼ 7) were added to STEEN Solution (XVIVO Perfusion, Goteborg, Sweden) to achieve a perfusate hemoglobin concentration of 40 g/liter. RESULTS: The perfusate composition affected the preservation of systolic (T5 dP/dt max : RBCþPlasma ¼ 903  99, RBC ¼ 771  77, HBOCþPlasma ¼ 691  82, HBOC ¼ 563  52 mm Hg/sec; p ¼ 0.047) and diastolic (T5 dP/dt min : RBCþPlasma ¼ –574  48, RBC ¼ –492  63, HBOCþPlasma ¼ –326  32, HBOC ¼ –268  22 mm Hg/sec; p o 0.001) function, and the development of myocardial edema (weight gain: RBCþPlasma ¼ 6.6  0.9, RBC ¼ 6.6  1.2, HBOCþPlasma ¼ 9.8  1.7, HBOC ¼ 16.3  1.9 g/hour; p o 0.001) during EVHP. RBCþPlasma hearts exhibited less histologic evidence of myocyte damage (injury score: RBCþPlasma ¼ 0.0  0.0, RBC ¼ 0.8  0.3, HBOCþPlasma ¼ 2.6  0.2, HBOC ¼ 1.75  0.4; p o 0.001) and less troponin-I release (troponin-I fold-change T1–T5: RBCþPlasma ¼ 7.0  1.7, RBC ¼ 13.1  1.6, HBOCþPlasma ¼ 20.5  1.1, HBOC ¼ 16.7  5.8; p o 0.001). Oxidative stress was minimized by the addition of plasma to RBC and HBOC hearts (oxidized phosphatidylcholine compound fold-change T1–T5: RBCþPlasma ¼ 1.83  0.20 vs RBC ¼ 2.31  0.20, p o 0.001; HBOCþPlasma ¼ 1.23  0.17 vs HBOC ¼ 2.80  0.28, p o 0.001). http://www.jhltonline.org 1053-2498/$ - see front matter r 2014 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2014.09.021 E-mail address: dhfreed@ualberta.ca Reprint requests: Darren H. Freed, MD, PhD, University of Alberta Hospital, 2D4.34 WMC, 8440-112 St, Edmonton, AB, T6G 2B7 Canada. Telephone: 780-407-1959. Fax: 780-407-3672.