Sarin arrhythmias

GA, a unitary chemical munition, inhibits AChE, the enzyme responsible for the breakdown of the neurotransmitter ACh. When inhaled, its toxicity is half that of sarin. It depresses plasma and RBC-AChE activities significantly in the blood. At 20-25% of red blood cell AChE baseline, the effect of the nerve agent becomes noticeable. There is no evidence of systemic toxicity other than the cholinesterase activity (Parker et al, 1990 Munro et al, 1994). GA has not been shown to produce OPIDN except at extremely high doses. The cardiac effect of GA conforms to OP-caused arrhythmias and AV block. 

Sarin was involved in terrorist attacks in Japan (Okumura et al, 2003 Okudera, 2002). The increase in sympathetic and parasympathetic tone results in tachycardia, ST-segment modulation (Abraham et al, 2001), and arrhythmia. Inhibition of cholinesterase within the neuroeffector junction also affects nerve impulse transmission by direct action. Direct action on muscarinic or nicotinic ACh receptors (Somani et al, 1992) is observed when the blood level of sarin exceeds the micromolar level. Sarin inhibits RBC-AChE 80-100% as well as plasma-BChE between 30 and 50% (Grob and Harvey, 1958). It also binds to aliesterase, an enzyme that contributes to ester-link hydrolysis. 

Sarin exhibits OP-delayed cardiotoxicity. Allon et al (2005) suggest epinephrine-induced arrhythmias as a possible cause in cases of sarin intoxication. The hypothesis is supported by Khositseth et al (2005) who showed that epinephrine changes T-waves in the ECG where AT prolongation already exists. 

Well-known symptoms of sarin toxicity include miosis, hypersecretions, bradycardia, and fasciculations. However, the mechanism of organophosphate toxicity seems to involve conflicting actions. For example, mydriasis or miosis, and bradycardia or tachycardia may occur. Acute respiratory insufficiency is the most important cause of immediate death. Early symptoms include (i) tachypnea due to increased airway secretions and bronchospasm (a muscarinic effect), (ii) peripheral respiratory muscle paralysis (a nicotinic effect), and (iii) inhibition of respiratory centers (a CNS effect), all of which lead to severe respiratory deficiency. If left untreated at this stage, death will result. Cardiovascular symptoms may include hypertension or hypotension. Various arrhythmias can also occur, and caution is required when the QT interval is prolonged. In particular, if hypoxemia is present, fatal arrhythmias may occur with intravenous administration of atropine... 

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