Preservation of the donor heart: from basic science to clinical studies

Abstract

The methods of donor heart preservation are aimed at minimizing graft dysfunction caused by ischaemia-reperfusion injury (IRI) which inevitably occurs during the ex vivo transport interval. At present, the standard technique of heart preservation is cardiac arrest followed by static cold storage in a crystalloid heart preservation solution (HPS). This technique ensures an acceptable level of heart protection against IRI for <6 h. In clinical trials, comparable levels of myocardial protection against IRI were provided by various HPSs. The growing shortage of donor hearts is one of the major factors stimulating the development of new techniques of heart preservation. Here, we summarize new HPS formulations and provide a focus for optimization of the composition of existing HPSs. Such methods of donor heart preservation as machine perfusion, preservation at sub-zero temperature and oxygen persufflation are also discussed. Furthermore, we review experimental data showing that pre- and post-conditioning of the cardiac graft can improve its function when used in combination with cold storage. The evidence on the feasibility of cardiac donation after circulatory death, as well as the techniques of heart reconditioning after a period of warm ischaemia, is presented. The implementation of new techniques of donor heart preservation may contribute to the use of hearts from extended criteria donors, thereby expanding the total donor pool.

Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing

“…A variety of preservation solutions, such as ViaSpan (University of Wisconsin solution), Celsior, Custodiol histidine‐tryptophan‐ketoglutarate solution and, more recently, HypoThermosol (HTS), were developed taking these factors into consideration [15] and are commercially available today. These solutions showed to be effective for hypothermic storage of a large diversity of cells, tissues, and organs (including neonatal rat ventricular cardiomyocytes [16], renal cells [17], hepatocytes [18, 19], liver tissue [20], synthetic human epidermis tissue [21], kidney [22], pancreas [23], liver [20], and heart [24, 25]). Importantly, some of these formulations can be directly administered into patients, avoiding additional poststorage culture manipulations/costs and washing steps.…”

“…The time interval that a cardiac graft can be efficiently cold‐stored remains limited to 6 hours [25]. This finite time frame further limits donor heart supply, access, and utility.…”

Machine perfusion of thoracic organs

“…This method was designed at a time when donors were "ideal" and preservation periods were short. Up to date it remains the golden standard for preservation of heart (22,23) and lungs (24,25).…”

Ice, ice, maybe? Is it time to ditch the igloo cooler? Benefits of machine perfusion preservation of donor hearts

“…Presently, cardiac allograft preservation is by hypothermic static storage preservation (eg, ice chest, cold bucket, etc). This preservation method typically allows for up to 6 h total time between retrieval and implantation . As the number of patients bridged to transplant by ventricular assist devices continues to increase, so too does the surgical complexity.…”