Modulation Of The Inflammatory Response In The Abdominal Organ Donor

Optimal donor management may have favorable immunological consequences in addition to improving graft function. Recipients of living unrelated renal allografts (e.g., spousal donors), despite HLA disparity, have 1 and 5 year graft survival that is equivalent to grafts received from haploidentical donors. Thus, when injury associated with brain death, donor management and prolonged cold ischemia time is eliminated as in living unrelated donor transplants, HLA mismatch is considerably less significant in influencing long-term outcome. The impact of HLA match in cadaveric transplantation is also questionable. Recent evidence suggests that nonimmunologic injury sustained by the organ may predispose to a cascade of self-sustaining immunologic events resulting in increased likelihood of rejection and graft loss. Poor donor management with resultant graft injury may, therefore, serve to negate any potential benefit that derives from improved HLA matching.

Studies in animal models support the use of various agents to blunt nonimmunologic, nonspecific injury which can occur during the recovery process or result from reperfusion injury in the organ recipient. These agents include inhibitors of lipid peroxidation, antioxidants, free radical scavengers, nitric oxide modulation, protease inhibitors, prostaglandins, calcium channel blockers and monoclonal antibodies directed against adhesion molecules. Unfortunately, the limited clinical studies to date examining the use of selected agents in humans is less than encouraging. Faults with study design and inability to control for the great number of donor variables that eventually contribute to outcome may account for conflicting data or apparent lack of efficacy. Failure to standardize organ preservation techniques, i.e., cold storage versus pulsatile perfusion, will further confound interpretation of these studies.

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