sodium-nitrite and Shock

Nitrite (NO(2)(-)), previously viewed as a physiologically inert metabolite and biomarker of the endogenous vasodilator NO, was recently identified as an important biological NO reservoir in vasculature and tissues, where it contributes to hypoxic signaling, vasodilation, and cytoprotection after ischemia-reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin, deoxymyoglobin, xanthine oxidase, mitochondrial complexes, or NO synthase (NOS). We show that nitrite treatment, in sharp contrast with the worsening effect of NOS inhibition, significantly attenuates hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction, and mortality in a mouse shock model induced by a lethal tumor necrosis factor challenge. Mechanistically, nitrite-dependent protection was not associated with inhibition of mitochondrial complex I activity, as previously demonstrated for ischemia-reperfusion, but was largely abolished in mice deficient for the soluble guanylate cyclase (sGC) alpha1 subunit, one of the principal intracellular NO receptors and signal transducers in the cardiovasculature. Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were required. In conclusion, we show that nitrite can protect against toxicity in shock via sGC-dependent signaling, which may include hypoxic vasodilation necessary to maintain microcirculation and organ function, and cardioprotection.

Topics: Animals; Female; Guanylate Cyclase; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mitochondria; Nitric Oxide; Nitric Oxide Synthase Type III; Reactive Oxygen Species; Receptors, Cytoplasmic and Nuclear; Shock; Sodium Nitrite; Soluble Guanylyl Cyclase; Tumor Necrosis Factor-alpha

A case of attempted homicide by cyanide ingestion is reported. The victim, a 19-year-old woman, unknowingly ingested cyanide and presented to the Emergency Department unresponsive, in shock, and in profound metabolic acidosis. The differential diagnosis of this presentation and the patient's successful treatment are reviewed. The important management issues surrounding the treatment of cyanide poisoning are discussed.

Topics: Acidosis; Acute Disease; Adult; Antidotes; Cyanides; Diagnosis, Differential; Electrocardiography; Emergency Treatment; Female; Fluid Therapy; Homicide; Humans; Respiration, Artificial; Shock; Sodium Nitrite; Spouse Abuse; Thiosulfates

We studied the effects of nitric oxide (NO) solution and acidified sodium nitrite (NaNO2), which produces NO, in splanchnic artery occlusion (SAO) shock in cats. NO is thought to be endothelium-derived relaxing factor (EDRF), a labile substance having several potentially valuable biological effects. Anesthetized cats subjected to total occlusion of the celiac, superior mesenteric, and inferior mesenteric arteries for 120 min, followed by reperfusion, usually died approximately 60 min after reperfusion. NO infusion significantly improved survival time in SAO-shock cats compared with those receiving vehicle (P less than 0.005). Administration of NO also attenuated the increase in plasma activities of the lysosomal hydrolase cathepsin D (P less than 0.05), total amino-nitrogen (P less than 0.001), and of the cardiotoxic peptide, myocardial depressant factor (MDF) (P less than 0.001). SAO-shock cats treated with NaNO2 at pH 2.0 also exhibited lower plasma cathepsin D (P less than 0.001), amino-nitrogen (P less than 0.05), and MDF activities (P less than 0.01), and survival time was also significantly improved (P less than 0.02). The same dose of NaNO2 infused at pH 7.4 failed to exert any significant protective effect. These results indicate that NO exerts beneficial effects in SAO shock in cats and suggest that exogenously administered NO may be a potentially useful therapeutic agent in splanchnic ischemic shock, probably via a cytoprotective rather than a vasodilator effect.

Topics: Amines; Animals; Biomarkers; Blood Pressure; Cathepsin D; Cats; Male; Nitric Oxide; Nitrites; Shock; Sodium Nitrite; Splanchnic Circulation; Time Factors