Repletion of S-nitrosohemoglobin improves organ function and physiological status in swine after brain death.
OBJECTIVE
To determine if reduction in nitric oxide bioactivity contributes to the physiological instability that occurs after brain death and, if so, to also determine in this setting whether administration of a renitrosylating agent could improve systemic physiological status.


BACKGROUND
Organ function after brain death is negatively impacted by reduced perfusion and increased inflammation; the magnitude of these responses can impact post-graft function. Perfusion and inflammation are normally regulated by protein S-nitrosylation but systemic assessments of nitric oxide bioactivity after brain death have not been performed.


METHODS
Brain death was induced in instrumented swine by inflation of a balloon catheter placed under the cranium. The subjects were then serially assigned to receive either standard supportive care or care augmented by 20 ppm of the nitrosylating agent, ethyl nitrite, blended into the ventilation circuit.


RESULTS
Circulating nitric oxide bioactivity (in the form of S-nitrosohemoglobin) was markedly diminished 10 hours after induction of brain death-a decline that was obviated by administration of ethyl nitrite. Maintenance of S-nitrosohemoglobin was associated with improvements in tissue blood flow and oxygenation, reductions in markers of immune activation and cellular injury, and preservation of organ function.


CONCLUSIONS
In humans, the parameters monitored in this study are predictive of post-graft function. As such, maintenance of endocrine nitric oxide bioactivity after brain death may provide a novel means to improve the quality of organs available for donation.
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Basil M
BM
Yurcisin
Tara E
TE
Davison
Syreena M
SM
Bibbs
Bradley H
BH
Collins
Jonathan S
JS
Stamler
James D
JD
Reynolds
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001784:Blood Gas Analysis; D001926:Brain Death / Q000097:blood / Q000503:physiopathology*; D006454:Hemoglobins / Q000378:metabolism*; D007677:Kidney Function Tests; D016014:Linear Models; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D020858:Tissue and Organ Harvesting
D015415:Biomarkers; D006454:Hemoglobins; D009573:Nitrites; C103574:S-nitrosohemoglobin; D009569:Nitric Oxide; C032712:ethyl nitrite