No evidence of NO-induced damage in potential donor organs after brain death.
Brain death induces multiple-organ dysfunction, with undesirable consequences for organ transplantation. However, the mechanisms are not completely clear. In the hearts, lungs, livers, and kidneys of rats, we investigated whether brain death leads to changes in nitric oxide (NO) production or to the formation of nitrotyrosine (the footprint of peroxynitrite, formed from NO and superoxide) or to lipid peroxidation products. To produce a rat model of brain death, we inflated a subdurally placed balloon catheter. We used the Griess reaction to assay plasma nitrite and nitrate. Proteolytic digestion followed by high-performance liquid chromatography (HPLC) with electrochemical detection determined nitrotyrosine formation in the tissues. Tissues were also examined immunohistochemically with anti-nitrotyrosine antibody. We used a thiobarbituric acid method to assay lipid peroxidation. An intense, transient hemodynamic activation occurred at the onset of brain death (heart rate, 496 beats/min; mean arterial pressure (AP), 181 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 of nitrite plus nitrate remained unchanged 2 hours after brain death (32.8 +/- 1.5 vs 31.3 +/- 2.2 micromol/liter at zero time). Neither HPLC nor immunohistochemistry detected significant nitrotyrosine formation in the tissues. We detected no increase in lipid peroxidation products.Our results indicate that changes in the generation of reactive nitrogen and active oxygen species do not play an important role in post-brain-death organ dysfunction, at least not at the early stage.
Halejcio-Delophont
P
P
Department of Physiology, Tokai University, School of Medicine, Boseidai, 259-1193, Kanagawa, Japan. delophon@is.icc.u-tokai.ac.jp
Hoshiai
K
K
Fukuyama
N
N
Nakazawa
H
H
D000818:Animals; D015415:Biomarkers; D001926:Brain Death / Q000378:metabolism / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D016027:Heart Transplantation; D006439:Hemodynamics / Q000502:physiology; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013858:Thiobarbiturates / Q000378:metabolism; D014019:Tissue Donors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism
D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D013858:Thiobarbiturates; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C029684:thiobarbituric acid