Summer 1996 Volume 3, Number 1

CARDIAC TRANSPLANTATION

Evolving Strategies for Long-Term Organ Preservation

A shortage of suitable allograft organs currently restricts the frequency of organ transplantation, particularly cardiac transplantation. Public awareness efforts may now have reached their peak effectiveness, and presumed consent legislation, whereby any brain-dead, beating heart cadaver is assumed to be a donor, is probably not politically feasible in this country. Prospective studies of high-risk donors, or donors with contraindications or relative contraindications according to established guidelines, are increasingly being advocated as a means to increase the number of cardiac donors. This approach, however, is unlikely to yield anything like the number of cardiac allografts truly needed. On the other hand, some donor hearts are not utilized because of lack of a suitable recipient in the region. In these and other cases, extended preservation (greater than six hours) could provide enormous benefit.

In 1990, Storey and Storey described adaptive mechanisms permitting animals to freeze during the winter.¹ These mechanisms involve supercooling, stabilizing the liquid state at subzero temperatures. Increased intracellular glucose concentrations, high ATP levels, "antifreeze proteins" and other mechanisms allow animals to survive "controlled" freezing, a process which minimizes the formation of ice crystals and their damaging effects on cells.

In 1993, El-Gamel et al² first reported successful whole organ (cardiac) preservation for transplantation using subzero temperatures. They developed a cardioplegic solution with high glucose and ATP levels and reported that rat hearts stored for 4 hours at -9° C could be successfully transplanted heterotopically, with return of the normal electrocardiogram and contractility. Light and electron microscopy were performed, but abnormalities (including mitochondrial damage) were reportedly rare. Letsou et al later extended this method of cooling to 12 hours with excellent results at one week, at which time the animals (rats) were sacrificed.³ Current research focuses on metabolic parameters at these very low temperatures in an effort to discern the mechanism(s) of this potentially powerful adjunctive strategy for whole organ transplantation. If intermediate-term shelf availability of transgenically-derived cardiac xenografts can be achieved through the use of this organ freezing technology, the potential impact in cardiac surgery would be considerable.

John C. Baldwin, MD
Department of Surgery
Baylor College of Medicine
The Methodist Hospital
Houston, Texas

REFERENCES

1. Storey KB, Storey JM. Frozen and alive. Scientific American, December 1990, pp 62-67.
2. El-Gamel A, Lui G, Cole G, Condos S, Baldwin JC. Successful freezing preservation and transplantation of mammalian hearts stored in hypertonic glucose solution at high sub-zero temperature. Abstract presented and published, Thoracic Transplantation Meeting, Universitat Ruhr, Germany, 1993.
3. Letsou, GV, Liu W, Zarif A, Cole G, El-Gamel A, Baldwin JC. Cardiothoracic successful transplantation of frozen hearts after 12 hours storage. Abstract presented and published, Horizons in Transplantation, Grand Cayman Island, 1996.

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