Medical Aspects of Chemical Warfare (2008) - The Black Vault

Cyanide PoisoningVoltage (mV)40200-20-40-60-800 50 100 150 200 250 300Time (ms)Fig. 11-9. Blocking the anionic, cell swelling-activatedchloride current can restore the morphology of the cyanideaffected action potential, the curve at the left (red curve), tothe unaffected state. A partial block moves the curve towardthe right (blue curve) and also restores the resting potential.A total block (green curve) achieves complete restoration tothe normal.ing cyanide-induced electropathophysiology. Two ofthe more important activated currents are the I KATP,because of the decline in the ATP stores, and I Cl,swell,when the cell volume is modulated. Change in cellularion concentrations, also an important aspect of cyanidetoxicity, includes calcium overload, which causes theactivation of K + channels. 205 Rise in [Na + ] iand [Ca 2+ ] ienhance the I Kscurrent, which is activated at voltagevalues much higher than for I Kr. I Kris reduced by acidificationand the presence of external divalent cations,noticeable in cyanide-affected tissue. The results werevalidated against the ECG of a subject under cyanideintoxication (see Figure 11-6). 195 Figures 11-7 to 11-9demonstrate the impact of simulated changes in eachcurrent parameter. Each simulation incorporates establishedconductance ratios and previous modelingresults. 206–210Disturbances of the energy homeostasis and ionconcentrations in cardiac tissue from cyanide resultin reversal of the normal directions and magnitudechanges in cellular membrane currents. These effectsin turn change the morphology of the action potentialand ECG. These disturbances eventually lead to ventricularfibrillation, the usual endpoint in the effect ofcyanide on the heart. The negative trending T-wave inthe ECG indicates pathological behavior, the abnormalrepolarization of the ventricle.The computer simulation demonstrates that pharmacologicintervention has the potential to reverseor minimize the impact of cyanide on cardiac electrophysiology.Further research is needed to validatethe conclusions of simulation. Simulation can focusresearch and also provide leads for successful interventions.However, no drugs have yet been assessedfor their specific utility to reverse cyanide-inducedperturbations in cardiac physiology. Oxygen clearlyenhances antidotal efficacy, and it is possible that drugsto enhance delivery of oxygen into the mitochondriawill soon improve cardiac recovery.Neurological/Psychological Responses to Cyanide and Its CountermeasuresExplicit understanding of the specific effects ofcyanide exposure on the neuropsychology of humansor animals is limited. Impact would be expected, however,based on understood pathophysiology. Usingvarious animal models, alterations have been observedin learning, sensory responses, and neurologic reflexesafter exposure to sublethal doses of cyanide. Thesedata have been reviewed elsewhere 176 and will not befurther discussed in this clinically oriented review.Unfortunately, EEG recordings in humans haveonly occasionally been reported in cases of known orsuspected chronic cyanide toxicity. Sandberg describeda case study of suspected chronic cyanide exposure ina goldsmith apprentice who used KCN for cleaninggold articles. 211 The patient presented with headache,general malaise, and paresis in the left arm and leg.Blood cyanide was mildly elevated at 10 to 12 µg per100 mL of blood, and the EEG was described as exhibiting“diffuse frontal theta activity,” a nonspecificfinding. Treatment consisted of physical therapy andhydroxocobalamin therapy. After several months,blood cyanide levels dropped to 2 to 3 µg per 100 mLof blood, the EEG normalized, and paresis diminished,suggesting a diagnosis of chronic cyanide exposure.Diffuse frontal theta activity in the EEG is not specificto cyanide exposure, however; it has also been reportedin a group of 13 people who worked with various toxicsubstances. 212 Zaknun et al also report EEG findingsof diffuse, abnormal beta activity more pronouncedin frontal and front-temporal regions but no focalepileptic activity in the case summarized previously. 163Animal cyanide exposures provide evidence of transientEEG changes in the dog, 213 but in other studies,single or repeated IV infusions resulted in progressivedeterioration in the EEGs.The general psychological impact of terrorism and393