title: Recovery of donor hearts after circulatory death with normothermic extracorporeal machine perfusion.
abstract: OBJECTIVE
  A severe donor organ shortage leads to the death of a substantial number of patients who are listed for transplantation. The use of hearts from donors after circulatory death could significantly expand the donor organ pool, but due to concerns about their viability, these are currently not used for transplantation. We propose short-term ex vivo normothermic machine perfusion (MP) to improve the viability of these ischaemic donor hearts.
  
  
  METHODS
  Hearts from male Lewis rats were subjected to 25 min of global in situ warm ischaemia (WI) (37°C), explanted, reconditioned for 60 min with normothermic (37°C) MP with diluted autologous blood and then stored for 4 h at 0-4°C in Custodiol cold preservation solution. Fresh and ischaemic hearts stored for 4 h in Custodiol were used as controls. Graft function was assessed in a blood-perfused Langendorff circuit.
  
  
  RESULTS
  During reconditioning, both the electrical activity and contractility of the ischaemic hearts recovered rapidly. Throughout the Langendorff reperfusion, the reconditioned ischaemic hearts had a higher average heart rate and better contractility compared with untreated ischaemic controls. Moreover, the reconditioned ischaemic hearts had higher tissue adenosine triphosphate levels and a trend towards improved tissue redox state. Perfusate levels of troponin T, creatine kinase and lactate dehydrogenase were not significantly lower than those of untreated ischaemic controls. The micro- and macroscopic appearance of the reconditioned ischaemic hearts were improved compared with ischaemic controls, but in both groups myocardial damage and oedema were evident.
  
  
  CONCLUSIONS
  Our results indicate that functional recovery from global WI is possible during short-term ex vivo reperfusion, allowing subsequent cold storage without compromising organ viability. We expect that once refined and validated, this approach may enable safe transplantation of hearts obtained from donation after circulatory death.
authors.affiliation: Division of Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland herman.tolboom@usz.ch.
authors.forename: Herman
authors.initials: H
authors.lastname: Tolboom
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty and the Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zürich, Switzerland.
authors.forename: Asya
authors.initials: A
authors.lastname: Makhro
authors.affiliation: Department of Visceral and Transplant Surgery, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Rosser
authors.affiliation: Division of Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Wilhelm
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty and the Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zürich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bogdanova
authors.affiliation: Division of Cardiovascular Surgery, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Falk
mesh_terms: D000818:Animals; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D016027:Heart Transplantation; D008297:Male; D008954:Models, Biological; D015425:Myocardial Reperfusion; D009926:Organ Preservation / Q000379:methods*; D018384:Oxidative Stress; D051381:Rats; D020858:Tissue and Organ Harvesting; D019737:Transplants / Q000502:physiology*
keywords: Cardiac transplantation; Donation after circulatory death; Ischaemia–reperfusion; Machine perfusion; Organ preservation