[Frontiers in Bioscience 14, 2009-2009, January 1, 2009]

A review of studies relating to thyroid hormone therapy in brain-dead organ donors

Thyroid hormone therapy in brain-dead organ donors

David K.C. Cooper1, Dimitri Novitzky2, Winston N. Wicomb3, Murali Basker4, John D. Rosendale5, H. Myron Kauffman5

1Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, 2Tampa General Hospital Heart Transplantation Program, University of South Florida, Tampa, FL, 3Infectious Disease Research Institute, Seattle, WA, 4Department of Surgery, Geisinger Medical Center, Danville, PA, 5Research Department , United Network for Organ Sharing, Richmond, VA

TABBLE OF CONTENTS

1. Abstract
2. Introduction 3. Observations leading to the recognition of the deleterious effects of brain death on donor organs 4. Management of the potential organ donor in 1981
5. Studies of brain death in the experimental animal and human potential organ donor
5.1. Electrocardiographic
5.2. Hormonal
5.3. Hemodynamic
5.4. Myocardial energy stores
5.5. Myocardial histology
6. Studies to elucidate the mechanism of myocardial injury during brain death
7. Impairment of renal function following brain death
8. The Effects of brain death and 24 hours storage by hypothermic perfusion on donor heart function
9. Reversal of functional deterioration of the heart after brain death
9.1. Change from aerobic to anaerobic metabolism after brain death, and reversal following T3 therapy
9.2. Effect of hormonal therapy after brain death and storage of the heart
9.3. Reversal of functional deterioration of the heart in the brain-dead human potential donor by hormonal therapy 10. Subsequent studies on brain death and the effect of hormonal therapy
11. Wider adoption of hormonal therapy in the management of human brain-dead potential organ donors
12. Studies on the effects of T3 following myocardial ischemia and cardiopulmonary bypass in experimental animals
13. Studies on the effects of T3 following myocardial ischemia and cardiopulmonary bypass in patients undergoing open heart surgery
14. The Potential role of T3 in the treatment of both donor and recipient in cardiac transplantation
15. Experimental studies on T3 in regional myocardial ischemia
16. Acknowledgements
17. References

1. ABSTRACT

An acute decrease in cardiac performance can result from a reduced free triiodothyronine (FT3) level following (i) brain death (euthyroid sick syndrome), (ii) a period of cardiopulmonary bypass, and possibly (iii) regional or global myocardial ischemia. The two major pathophysiologic effects of brain death are (i) vascular injury associated with the hemodynamic consequences of the autonomic 'storm', and (ii) a generalized inhibition of mitochondrial function, which results in diminished organ function from the loss of energy stores from a rapid loss of circulating FT3. Deterioration of donor organ function can be reversed by hormonal replacement therapy, in which T3 plays a critical role. This results in (i) an increased number of organs being functionally acceptable, and (ii) increased early and intermediate graft survival. Cardiopulmonary bypass is associated with a reduction in the circulating level of FT3, and this can be associated with deterioration in cardiac function. The administration of T3 at the time of discontinuation of cardiopulmonary bypass reverses this state. In patients undergoing heart transplantation, T3 therapy to both donor and recipient is beneficial.