© 2013 Springer Science+Business Media New York. All rights reserved. In large animal experimental models, two major pathophysiologic effects of brain death have been described. (1) Tissue and vascular injury can result from the hemodynamic consequences of the autonomic storm. (2) A generalized inhibition of mitochondrial function that is associated with loss of energy stores and diminished organ function; this is associated particularly with the rapid loss of circulating free triiodothyronine (T3) and can be reversed by hormonal replacement therapy, in which T3 plays a critical role, although insulin and cortisol are also important. Replacement of energy stores and recovery of organ function in the potential donor results in an increased number of organs being functionally acceptable for transplantation. Although some studies did not detect abnormally low levels of thyroid hormones and/or question the advisability of administering T3 to the brain-dead animal, the preponderance of experimental data indicate that hormonal replacement therapy can be beneficial.