Organs procured from brain-dead organ donors undergo a series of noxious events which are initiated in the potential organ donor such as shock, hypoxia-ischemia, multiple transfusions etc. During the death of the brain, two types of injury occur: the first, as a result of the catecholamine storm and the second, as a result of the endocrine derangement and inhibition of the aerobic pathways. Further manipulation, such as prolonged cold preservation and reperfusion injury in the recipient, enhances potential endothelial-cellular damage of the transplanted organ.
In the donor, the initial tissue injury related to the catecholamine storm is associated with cellular ischemia and reperfusion.25 Catecholamines induce changes of the cytosolic calcium homeostasis, which is ATP dependent,26 affecting the voltage-gauged calcium entry into the cells,27 and have a key role in the excitation-coupling process in the heart, smooth muscle vascular tissue and neuropeptide release.28 The cytosolic Ca2+ increment precipitates activation of lipases, proteases and endonucleases. Activation of nitric oxide synthase leads to further cellular membrane injury induced by oxygen free radicals, the increment of adenosine (a byproduct of ATP catabolism) and activation of adenosine deaminase. Xanthine oxidase potentiates further the generation of cytotoxic oxygen free radicals inducing peroxidation of unsaturated fatty acids and lipids. The combination of Ca2+ and superoxide mediated tissue injury, which occurs simultaneously, is followed by the endocrine disintegration in the donor. As a result of this, there is inhibition of aerobic pathways,17,29 the cell can no longer metabolize mitochondrial fuels and the cellular energy charge is progressively reduced, eventually resulting in cellular death and possible to primary organ failure.
The aggressive management of the potential organ donor and the institution of hormonal therapy to brain-dead donors has been shown to reverse some of the brain death induced organ injuries, particularly to the heart and kidneys. Tri-iodothyronine plays a major role in restoring mitochondrial function, producting high energy phosphates and activating of various ATPases.30 Triiodothyronine mobilizes cytosolic Ca2+ in the sarcoplasmic reticulum31 and restores the Na+/K+ gradients. Thus, organs are in a more optimal condition for transplantation.
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