Honoring 50 Years of Clinical Heart Transplantation in Circulation: In-Depth State-of-the-Art Review

Josef Stehlik, MD, MPH; Jon Kobashigawa, MD; Sharon A. Hunt, MD; Hermann Reichenspurner, MD, PhD; James K. Kirklin, MD


Circulation. 2018;137(1):71-87. 

In This Article

Organ Preservation

At the time of heart procurement, the donor heart is arrested, and its contractile function resumes after reperfusion in the recipient's body. In the early days, organ preservation was achieved solely by hypothermic storage[15] based on experimental studies of Webb et al[15] and later Shumway's group.[6] In the 1970s, different cardioplegic solutions were developed for use in cardiac surgery and refined for their use in heart transplantation, with the goal of achieving rapid cessation of contractility and reducing the negative impact of ischemia on the heart. Extracellular cardioplegic solutions (eg, St. Thomas solution, Celsior) contain an electrolyte concentration ratio that results in cardiac arrest through inhibition of the Na+/K+-ATPase cell membrane pump. lntracellular solutions (eg, University of Wisconsin or histidine-tryptophan-ketoglutarate solution) have a low sodium concentration and a higher potassium content, which lead to cellular depolarization and diastolic cardiac arrest.[17] A recent meta-analysis suggested that organ preservation with University of Wisconsin solution is associated with less ischemic necrosis than Celsior and with better recipient survival compared with histidine-tryptophan-ketoglutarate cardioplegia.[18]

Despite advances in hypothermic organ preservation, allograft ischemic time continues to represent a strong risk factor for posttransplantation mortality, especially when it exceeds 4 hours.[19] This has been the key factor limiting the distance at which heart allografts can be procured and is the reason that routine donor-recipient human leukocyte antigen (HLA) matching has not been practical in heart transplantation.

Continuous perfusion of donor organs was proposed as an alternative to hypothermic organ preservation in the 1980s,[20] but logistical complexity retarded clinical application. Recently, new techniques allowing continuous normothermic perfusion have been tested clinically and show promise to extend safe procurement over long distances (see Current and Future Innovations in the Field of Heart Transplantation).[21]