Moderate hypothermia during ex vivo machine perfusion promotes recovery of hearts donated after cardiocirculatory death†.
OBJECTIVE
To establish the optimal machine perfusion temperature for recovery of hearts in a rodent model of donation after declaration of cardiocirculatory death (DCD).


METHODS
Hearts from male Lewis rats (n = 14/group) were subjected to 25 min of in situ warm (37°C) ischaemia to simulate DCD. They were then explanted and reperfused with diluted autologous blood for 60 min at 20, 25, 30, 33 or 37°C, after which they were stored at 0-4°C in Custodiol preservation solution for 240 min. Fresh-excised and cold-stored ischaemic hearts were used as controls. The viability of the different groups was assessed by comparing heart rate and left ventricular contractility in a Langendorff circuit, as well as perfusate levels of troponin-t and creatine kinase (CK), and myocardial levels of adenosine triphosphate (ATP) and reduced glutathione.


RESULTS
During ex vivo reperfusion, hearts in all groups resumed beating within minutes. The mean heart rate was highest in the 37°C group at 154.72 ± 33.01 beats × min(-1) (bpm), and declined in proportion to temperature to 39.72 ± 5.53 bpm at 20°C. Troponin-t levels were highest in the 37°C group (79.49 ± 20.79 µg/l), the values were significantly lower in all other reconditioned groups with a minimum of 12.472 ± 7.08 µg/l in the 20°C group (P < 0.0001). Tissue ATP levels ranged from 4.32 ± 1.71 µmol/g at 33°C to 4.59 ± 1.41 µmol/g at 30°C, all significantly higher than the mean ATP level of 1.41 ± 0.93 µmol/g in untreated ischaemic hearts (P < 0.0001). During Langendorff assessment, the mean heart rate and contractility of all groups were higher than those of cold-stored ischaemic hearts (P < 0.0001), yet not significantly different from those of fresh controls. The perfusate levels of troponin-t and CK, and myocardial levels of reduced-glutathione and ATP were not significantly different between groups.


CONCLUSIONS
Our results suggest that mild hypothermia during ex vivo reperfusion improves recovery of ischaemic hearts in a rodent DCD model.
Department of Cardiovascular Surgery, University Hospital Zürich, Zurich, Switzerland herman.tolboom@usz.ch.
Herman
H
Tolboom
Department of Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Veronika
V
Olejníčková
Department of Cardiovascular Surgery, University Hospital Zürich, Zurich, Switzerland.
Diana
D
Reser
Department of Paediatric Cardiology, Children's Hospital Zürich, Zurich, Switzerland.
Barbara
B
Rosser
Department of Cardiovascular Surgery, University Hospital Zürich, Zurich, Switzerland.
Markus J
MJ
Wilhelm
Institute of Veterinary Physiology, Vetsuisse Faculty and the Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
Max
M
Gassmann
Institute of Veterinary Physiology, Vetsuisse Faculty and the Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
Anna
A
Bogdanova
Department of Cardiovascular Surgery, University Hospital Zürich, Zurich, Switzerland.
Volkmar
V
Falk
D000818:Animals; D050377:Cold Ischemia / Q000379:methods*; D003643:Death; D004195:Disease Models, Animal; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D007036:Hypothermia, Induced / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods*; D009926:Organ Preservation / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D015996:Survival Rate; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting / Q000379:methods
Declaration of cardiocirculatory death; Heart transplantation; Ischaemia-reperfusion; Machine perfusion; Organ preservation