No evidence of NO-induced damage in potential donor organs after brain death

Background: Brain death induces multiple-organ dysfunction, with undesirabl e consequences for organ transplantation. However, the mechanisms are not c ompletely clear. In the hearts, lungs, livers, and kidneys of rats, we inve stigated whether brain death leads to changes in nitric oxide (NO) producti on or to the formation of nitrotyrosine (the footprint of peroxynitrite, fo rmed from NO and superoxide) or to lipid peroxidation products. Method: To produce a rat model of brain death, we inflated a subdurally pla ced balloon catheter, We used the Griess reaction to assay plasma nitrite a nd nitrate. Proteolytic digestion followed by high performance liquid chrom atography (HPLC) with electrochemical detection determined nitrotyrosine fo rmation in the tissues. Tissues were also examined immunohistochemically wi th anti-nitrotyrosine antibody. We used a thiobarbituric acid method to ass ay lipid peroxidation. Results: An intense, transient hemodynamic activation occurred at the onset of brain death (heart rate, 496 beats/min; mean arterial pressure (AP), 18 1 mm Hg; dP/dt(max), 11,500 mm Hg/sec). A constant hypotensive phase (mean AP, 50 mm Hg; dP/dt(max), 2,674 mm Hg/sec) followed. Plasma concentration o f nitrite plus nitrate remained unchanged 2 hours after brain death (32.8 /- 1.5 vs 31.3 +/- 2.2 mu mol/liter at zero time). Neither HPLC nor immunoh istochemistry detected significant nitrotyrosine formation in the tissues. We detected no increase in lipid peroxidation products. Conclusion: Our results indicate that changes in the generation of reactive nitrogen and active oxygen species do not play an important role in post-b rain-death organ dysfunction, at least not at the early stage.