Strategies To Minimize Ischemic Damage

The use of expanded donors including DCDs where periods of hypotension, hypoxia, and warm ischemia are encountered has provided us with opportunities to examine limits and develop strategies to help minimize damage. Although any period of warm ischemia had previously been thought to be inconsistent with organ donation, most organs will tolerate short periods of warm ischemia. Clinical experience with DCDs indicates that the kidneys, liver, pancreas and the lung will tolerate 30-60 minutes of warm ischemia and will still function adequately after transplantation. Administration of anticoagulation with heparin will help prevent small vessel occlusion and administration of pharmacologic agents, such as phentolamine, will help prevent vasospasm and enhance better flush and preservation of donor organs. Administration of nitric oxide precursors, such as L-arginine and nitroglycerin, either to donors or to preservation solutions has been shown experimentally to mitigate warm ischemic damage. Evidence is mounting supporting continuous machine perfusion of kidneys retrieved from expanded or DCDs. Warm ischemic damage can be limited and perhaps improved during cold preservation by continuously supplying substrates for repair and energy production upon reperfusion. Delayed graft function in machine-perfused kidneys retrieved from DCDs has been shown to be similar to DGF rates in cold-stored kidneys retrieved from ideal donors. Interestingly, brain death itself has been shown to have a detrimental effect on organ function after transplantation. In addition to the marked hormonal imbalances that occur with brain death, organ injury may occur by activating T lymphocytes and the inflammatory response via cytokine release. This response and subsequent organ injury has been shown experimentally to be abrogated by administration of agents that block T-cell costimulation. Since hypothermia-induced cell injury increases with increasing cold ischemia time, preservation times should be minimized, particularly in expanded donors. Likewise, in clinical transplantation, one of the only factors that can be controlled is preservation time and this should be minimized to prevent wastage of organs.

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