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A moderately detailed 3-D finite element model of the conductive anatomy of a canine thorax was used to examine the sensitivity of the results obtained during simulated transthoracic defibrillation to variations in skeletal muscle anisotropy and differing degrees of model inhomogeneity. The authors results suggest that the myocardial current density distribution is not particularly sensitive to the method used to model skeletal muscle anisotropy. However, anisotropy variations caused defibrillation parameters such as paddle to paddle impedance and threshold current to change by as much as 50%. The authors found a greater sensitivity in the myocardial current density and the defibrillation parameters to variations in model inhomogeneity. The changes observed in both depended substantially on paddle placement. This sensitivity to paddle placement highlights the difficulty in predicting how a reduction in anatomical detail will affect the myocardial current density distribution. In general, the authors found the defibrillation parameters to be more sensitive than the myocardial current density distribution to the variations in anatomical detail they examined.