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Pathophysiology of Brain Death and Effects of Hormonal Therapy in Large Animal Models

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The Brain-Dead Organ Donor

Abstract

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.

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Acknowledgments

DN, WNW, and DKCC thank their many former colleagues in Cape Town and Oklahoma City who contributed to the studies reviewed here. The histopathological studies were largely carried out by our late good friend and colleague, Alan Rose, of the Department of Pathology of the University of Cape Town, in whose memory we dedicate this chapter.

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Authors and Affiliations

  1. Department of Surgery, Tampa VA Medical Center, Tampa, FL, USA

    Dimitri Novitzky M.D., Ph.D., F.C.S. (SA)

  2. Infectious Disease Research Institute, Seattle, WA, USA

    Winston N. Wicomb Ph.D.

  3. Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    David K. C. Cooper M.A., Ph.D., M.D., M.S., D.Sc.(Med), F.R.C.S., F.A.C.S.

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  1. Dimitri Novitzky M.D., Ph.D., F.C.S. (SA)
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  2. Winston N. Wicomb Ph.D.
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Correspondence to David K. C. Cooper M.A., Ph.D., M.D., M.S., D.Sc.(Med), F.R.C.S., F.A.C.S. .

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  1. Tampa VA Medical Center, Surgery, University of South Florida, Bruce B. Downs Blvd 12901, Tampa, 33612, Florida, USA

    Dimitri Novitzky

  2. Thomas E. Starzl Transplantation Institu, Department of Surgery, University of Pittsburgh Medical Center, Lothrop Street 200, Pittsburgh, 15213, Pennsylvania, USA

    David K C Cooper

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Novitzky, D., Wicomb, W.N., Cooper, D.K.C. (2013). Pathophysiology of Brain Death and Effects of Hormonal Therapy in Large Animal Models. In: Novitzky, D., Cooper, D. (eds) The Brain-Dead Organ Donor. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4304-9_7

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