Enhancing Public Health Preparedness for a Terrorist Attack Involving Cyanide

Eckstein, Marc

doi:10.1016/j.jemermed.2007.03.040

Cited by 28 publications

(19 citation statements)

References 14 publications

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“…Cyanide is a toxic chemical that has been used as a weapon of war and also as means of terrorist attacks on civilian populations [25]. It inhibits the respiratory chain, blocking the utilization of oxygen and affecting mitochondrial function [17].…”

Section: Discussionmentioning

confidence: 99%

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Wang

Lucca

et al. 2010

J Neuroinflammation

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BackgroundActivated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis.MethodsCultured primary cortical neurons from embryonic Sprague-Dawley rats were assigned one of four groups: control, DAF treatment alone, hypoxic, or hypoxic treated with DAF. Hypoxic cultures were exposed to NaCN for 1 hour, rinsed, followed by 24 hour exposure to 200 ng/ml of recombinant human DAF in normal medium. Human DAF was used in the present study and it has been shown to effectively regulate complement activation in rats. Neuronal cell function, morphology and viability were investigated by measuring plateau depolarization potential, counting the number dendritic spines, and observing TUNEL and MTT assays. Complement C3, C3a, C3a receptor (R) production, C3a-C3aR interaction and MAC formation were assessed along with the generation of activated caspase-9, activated caspase-3, and activated Src.ResultsWhen compared to controls, hypoxic cells had fewer dendritic spines, reduced plateau depolarization accompanied by increased apoptotic activity and accumulation of MAC, as well as up-regulation of C3, C3a and C3aR, enhancement of C3a-C3aR engagement, and elevated caspase and Src activity. Treatment of hypoxic cells with 200 ng/ml of recombinant human DAF resulted in attenuation of neuronal apoptosis and exerted significant protection against neuronal dendritic spine loss and plateau depolarization reduction. Furthermore, treatment with DAF resulted in decreased accumulation of C3a, MAC, C3a-C3aR interaction, caspase-9, activated caspase-3, and pTyr416-Src (activated Src) tyrosine kinase.ConclusionDAF was found to reduce neuronal cell death and apoptosis in NaCN induced hypoxia. This effect is attributed to the ability of DAF to limit complement activation and inhibit the activity of Src and caspases 9 and 3. This study supports the inhibiting of complement as a neuroprotective strategy against CNS ischemia/reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Wang

Lucca

et al. 2010

J Neuroinflammation

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“…Each patient exposed to toxic amounts of cyanide would require an antidote quickly to prevent toxic manifestations and death (Eckstein, 2007). First, cyanide is plentiful and readily available in the United States and other countries as it is easily obtainable from both industrial use and from research laboratories.…”

Section: Cyanide As a Terrorist Agentmentioning

confidence: 99%

“…Then in November 2003, the U.S. Department of Homeland Security released information that al-Qaeda terrorists had developed a mechanism to disperse cyanide gas through indoor ventilation systems (Eckstein, 2007). In 1993, a perpetrator of the World Trade Center bombing indicated in court that he had planned on using cyanide to create a lethal gas cloud.…”

Section: Cyanide As a Terrorist Agentmentioning

confidence: 99%

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Hydroxocobalamin (Cyanokit)

Jones¹

2008

Advanced Emergency Nursing Journal

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Cyanide is a lethal poison that is widely available from many sources throughout the world. It has been used as a suicide and homicide agent throughout history and is a likely agent for terrorist attacks due to its chemical profile. Although rarely encountered, cyanide can be quickly fatal if not treated immediately with a cyanide antidote. Until recently, the only cyanide antidote available in the United States was the cyanide antidote kit, which has the risk of causing significant adverse effects in many patients. However, hydroxocobalamin (Cyanokit) was recently approved in the United States for the treatment of known or suspected cyanide toxicity. This article reviews cyanide toxicity and the place in therapy for hydroxocobalamin as a cyanide antidote.

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“…It can be made relatively easily, and terrorists could poison food or medicines or detonate a cyanide bomb in an enclosed space (4;5). Thus, cyanide exposure can occur under a variety of situations and mass casualties are possible.…”

Section: Introductionmentioning

confidence: 99%

Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection

Bebarta

Brittain

Chan

et al. 2017

Annals of Emergency Medicine

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Study Objective The two antidotes for acute cyanide poisoning in the United States must be given by intravenous injection. In the pre-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study was to determine if sodium nitrite and sodium thiosulfate are effective cyanide antidotes when given by intramuscular injection. Methods We used a randomized, non-blinded, parallel group study design in three mammalian models: cyanide gas inhalation in mice, with treatment post exposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all three models were lethal in the absence of therapy. Results We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the two drugs rescued 73% of the rabbits and 80% of the pigs. In all three species, survival in treated animals was significantly better than in control animals (log rank test, p < 0.05). In the pigs, the drugs attenuated a rise in the plasma lactate concentration within five minutes post-antidote injection (difference: plasma lactate, saline-versus nitrite-thiosulfate-treated 1.76 [95% confidence interval 1.25-2.27]). Conclusion We conclude that sodium nitrite and sodium thiosulfate given by intramuscular injection are effective against severe cyanide poisoning in three clinically relevant animal models of prehospital emergency care.

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Enhancing Public Health Preparedness for a Terrorist Attack Involving Cyanide

Cited by 28 publications

References 14 publications

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Hydroxocobalamin (Cyanokit)

Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection

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