Abstract
In preclinical studies, infusion of sodium nitrite delivers nitric oxide (NO) as treatment of vasospasm after subarachnoid hemorrhage. We evaluated safety and toxicity of intravenous nitrite administration in healthy volunteers infused with increasing doses of sodium nitrite for 48 h. Twelve volunteers (5 men, 7 women; mean age was 38.8 years, range 27–56 years) participated in the study. The starting sodium nitrite dose was 4.2 mg/kg/h, and it was doubled for each subsequent volunteer up to a maximal dose of 533.8 mg/kg/h at which a clinically silent dose-limiting toxicity (DLT) was observed. Toxicity included a transient decrease of mean arterial blood pressure or asymptomatic increase of methemoglobin level above 5%. The maximal tolerated dose (MTD) was 267 mg/kg/h. S-Nitrosothiols increased significantly in plasma, confirming in vivo sodium nitrite reduction to NO and encouraging its use against vasospasm and ischemia-reperfusion injury to the brain, kidneys, liver, and heart.
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Acknowledgment
The Intramural Research program of the National Institute of Neurological Disorders and Stroke at the NIH supported this research. I appreciate the support and dedication of the Surgical Intensive Care Unit and Vascular Access Service staff of the Clinical Center at the NIH.
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Results of this study has been published in Pluta et al. [10].
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I declare that I do not have conflict of interest.
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© 2013 Springer-Verlag Wien
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Pluta, R.M. (2013). Prolonged Intravenous Infusion of Sodium Nitrite Delivers Nitric Oxide (NO) in Humans. In: Zuccarello, M., Clark, J., Pyne-Geithman, G., Andaluz, N., Hartings, J., Adeoye, O. (eds) Cerebral Vasospasm: Neurovascular Events After Subarachnoid Hemorrhage. Acta Neurochirurgica Supplement, vol 115. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1192-5_11
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DOI: https://doi.org/10.1007/978-3-7091-1192-5_11
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