Editorials and Perspectives: Analysis and Commentary
Heart transplantation is still the gold standard to treat terminal heart insufficiency. A major limitation is donor shortage: the discrepancy between available organs and patients on the waiting lists increases continuously during the last two decades. Even the increasing use of assist device systems could not lead to lesser demand of donor hearts.
Various efforts may increase the donor pool, which include the optimizing of brain-dead donors, increased used of marginal donors, and the extension of donor criteria as well as the increase of safe cardiac preservation times. It was shown that donor brain death significantly impairs cardiac function, which may lead to exclusion of organs from transplantation. Improved management strategies including adequate volume substitution and hormone replacement therapy can retrieve at least some of these organs for cardiac transplantation (1). In the last years, accumulating evidence shows that the transplantation of so-called marginal organs is feasible with acceptable to good clinical outcomes (2). Especially these groups of potential donor hearts, which are the majority of the offered organs in certain regions, would profit from improved cardiac preservation strategies.
Therefore, recent research activities focus on the improvement of existing cardiac preservation solutions or the development of novel preservation strategies. Currently, it was shown that the modification of one of the most commonly used cardiac preservation solution histidine-tryptophan-ketoglurate (Custodiol; Dr F. Köhler Chemie GmbH, Bensheim, Germany) improves postischemic cardiac and vascular function (3) and may eligible for longer preservation times up to 12 hr. This solution is currently under clinical investigation.
A complete different concept of cardiac preservation is continuous blood perfusion of donor organs. Some years ago, the company Transmedics introduced the Organ Care System. First clinical experience showed that continuous blood perfusion of donor hearts with subsequent successful transplantation is feasible. Although currently a clinical trial (PROCEED II) is under way, until now, no scientific data have been published, which showed a superiority of this concept in comparison to standard care or any additional advantage. Furthermore, the Organ Care System is extremely expensive (ca. (euro)200,000 [U.S. $252,080] device costs plus ca. (euro)40,000 [U.S. $37,812] material costs per each heart procurement) and needs significantly more human resources, which—in my opinion—precludes the use of this system in the clinical routine.
Under these circumstances, alternative cardiac preservation strategies may significantly contribute to the improvement of graft quality and outcomes after heart transplantation. In the present article of Kato et al. (4), a novel method of subzero storage is described. The idea to preserve organs at subzero temperatures has been already discussed in the mid seventies (5). Nevertheless, for 40 years, less then a dozen scientific reports have been published in this topic. Although the advantages of supercooling are obvious, as we also know from the food industry, some adverse effects and technical issues precluded this concept from being used clinically. Freeze temperatures may destroy the tissue of the donor organs; therefore, different cryoprotectants such as polyethylene glycol or antifreeze protein had to be used to protect donor tissue, which in turn may have adverse effects during rewarming and after transplantation. The novel supercooling system, which is described in the present study, uses variable magnetic field to prevent crystallization of water and thereby tissue damage. In this system, the use of cryoprotectants is not necessary, and therefore, related adverse effects can be excluded. The application of this system led to an improved functional recovery and better preserved high-energy phosphate contents in a Langendorff model. Whether the donor hearts can be taken from the deep freezer in the near future remains unclear. Nevertheless, this promising new technology deserves further evaluation in more clinically relevant models.
1. Szabó G. Physiological changes after brain death. J Heart Lung Transplant
2004; 23 (9 suppl): S223.
2. Witwer T, Wahlers T. Marginal donor grafts in heart transplantation: lessons learned from 25 years of experience. Transpl Int
2008; 21: 113.
3. Loganathan S, Radovits T, Hirschberg K, et al.. Effects of Custodiol-N, a novel organ preservation solution .on ischemia/reperfusion injury. J Thorac Cardiovasc Surg
2010; 139: 1048.
4. Kato H, Tomita S, Yamaguchi S, et al.. Subzero 24-hour nonfreezing rat heart preservation: A novel preservation method in a variable magnetic field. Transplantation
2012; 94: 473.
5. Hobbs KE. The current status of sub zero organ preservation. Proc R Soc Med
1975; 68: 290.