http://journals.lww.com/annalsofsurgery/Abstract/publishahead/Repletion_of_S_Nitrosohemoglobin_Improves_Organ.98557.aspx
Abstract
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.
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