Simulation of acetylcholine cardiac overload caused by Soman, a cholinesterase inhibitor

Organophosphates (OPs) are known to produce not only atrial bradyarrhythmia, but also serious conduction cardiac arrhythmias that can lead to death. Simulating these types of arrhythmias on various cardiac structures may provide a rational understanding of which structure would most contribute to the pathologic cardiac picture, and thus should allow for improved therapy. OP-produced acetylcholine (ACh) overload of the heart was simulated by its effect on the sino-atrial (SA) node, the Purkinje fiber, and the ventricles of the rabbit. The observed pathology as a function of ACh concentration was studied in terms of the divergence of the membrane currents and the action potential from baseline. Based on results of simulations with extracellular K₀⁺ concentrations, a new model for soman-induced cardiac arrest is proposed