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

Medical Aspects of Chemical WarfareFig. 22-4. Effects of soman (GD) on acetylcholinesterase(AChE) activity in whole blood from human volunteerswho had taken pyridostigmine bromide (PB; 30 mg tablet).Blood was drawn 2.5 hours after dosing, when red blood cell(RBC) AChE is maximally inhibited by PB (blue bar, left ofdashed line). After GD exposure, PB and GD were removedusing a C 18chromatography spin column (postcolumn treatment).The PB-protected (carbamylated and sequestered)AChE activity returned by 6 hours postcolumn. Green barsshow the correlation between the initial percent inhibition ofRBC-AChE by PB (solid red line) and the subsequent returnof AChE activity due to decarbamylation of the protectedenzyme after removing PB and GD (green bars). While therewas about 29.9% inhibition of RBC-AChE by PB before GDexposure (blue bar with arrow), at 24 hours (the green barwith arrow) there was about 33.7% return in activity afterthe column, demonstrating protection of RBC-AChE by PBpretreatment. Error bars represent the mean plus or minusthe standard error of the mean.AChE: acetylcholinesteraseGD: somanPB: pyridostigmine bromideRBC: red blood cellAChE activity (U/mL)3.02.52.01.51.00.50.0control, no GD(placebo)29.9% Inhibition by PB (carbamylated AChE)70.1% AChE activity remainingGD (1μM, 10 min)0 min30 min33.7% AChE activity66.3% Inhibition60 min3 h6 h24 h24 h, no GD1. Precolumn1. treatment2. Postcolumnby Hup A increased, compared to PB. Thus, Hup A ishighly effective in protecting RBC-AChE from ex-vivosoman exposure.As a pretreatment, Hup A is a specific and highlyselective RBC-AChE inhibitor, with serum BChE remainingunaffected at physiological concentrations. 75Thus, after exposure to an OP nerve agent, the effectivebioscavenging capacity for serum BChE is preserved. 76This lack of BChE inhibition represents an additionaladvantage of Hup A in preventing OP toxicity, andhelps explain increased tolerance of Hup-A–pretreatedanimals to soman in comparison to animals pretreatedwith PB.Studies of toxicology and treatment for nerve agentexposure have predominantly focused on lethal andsupralethal doses of the agent. The acute and long-termeffects of sarin in humans were well documented followingthe terrorist attacks in Japan in 1994 and 1995.Several severely poisoned victims (in cardiopulmonaryarrest or in comas with generalized convulsions)had plasma BChE activities of 20% of normal (80%inhibited). 77 However, information regarding the delayedor long-term subclinical effects of low-level ortrace amounts of sarin and other nerve agents, insecticides,and a variety of environmental chemicals (towhich individuals may be asymptomatic) is relativelyscarce, both in military and civilian environments.Potential scenarios can be envisioned in which lowor trace exposures become significant. Given the possibilityof urban terrorism involving chemical warfareOP agents, federal, state, and local authorities nowhave a variety of sensitive and accurate ChE and OPdetection assays to initiate appropriate containment,decontamination, and treatment measures.SULFUR MUSTARDBackgroundAnalysis of specimens, such as blood or urine, followinga suspected chemical warfare agent exposurehas been rare. Historically, biomedical samples collectedafter a suspected exposure were used for standardclinical assays and not preserved for later analysis.Highly sophisticated analytical methods required toverify chemical warfare agent exposure were not apart of the clinical laboratory methods inventory. More706