After visiting Professor Bahnson in 1983 (and his 2 key coworkers at that time, Dr. Hardesty and Dr. Griffith), Stig Steen established an orthotopic heart transplantation model on pigs in his laboratory at Lund University Hospital. With this model, all new heart preservation methods have been tested. Cold ischemic preservation of hearts with all the commonly used solutions, e.g. St. Thomas with different modifications, UW and Celsior give fair preservation of healthy pig hearts taken from pigs with intact brains of 8 hours, but not for 12 hours. After 12 hours of cold ischemic storage, the vascular endothelium of the coronary arteries is dysfunctional, and during the reperfusion multiple infarctions develop gradually in the heart (from 1991-99 we published 11 original papers in the Annals of Thoracic Surgery about preservation of the vascular endothelium, including in the pig heart). In clinical heart transplantation the time for safe heart preservation is 4-5 hours, and cold ischemic storage is still the only method in routine use anno 2009.
It stood clear to us in 1999 that a breakthrough in heart preservation cannot be accomplished without a perfect preservation of the vascular endothelium of the heart. The heart differ from the kidneys, liver and lungs, since for each heart beat, the vascular endothelium is squeezed by the heart muscle, and this strong mechanical trauma is too much for dysfunctional endothelial cells, that are disconnected from their basal membrane, and may cause multiple microembolis. Furthermore, the reduced endothelium-dependent relaxation capacity causes uneven reperfusion eliciting malign arrhythmias.
In parallel with the heart preservation research, we developed an ex-vivo reconditioning model for dysfunctional lungs, introducing into clinical practice the use of rejected donor lungs that we had reconditioned by perfusion with oxygenated purified erythrocytes (Lancet 2001; 357:825-29). We have now modified that method for the heart – the first prototype is shown in the picture below.
RESEARCH POWER AND FUTURE POSSIBILITIES
We have at the present moment done 70 orthotopic heart transplantations with this new method. The donor heart is obtained from a brain dead pig, kept in ex-vivo perfusion for 24 hours, then orthotopic transplantation is done. Weaning from ECC is accomplished within 1 hour without the need of any heart stimulating drugs, and the transplanted pigs are circulatory stable during the observatory period of 24 hours. We are now seeking ethical permission to start long-time survival experiments.