That bites!: the transport of Bothrops asper venom in leg
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Abstract
Snake venom has been known to be a deadly toxin for centuries. Although many studies about the dangerous effects of snake venom have been conducted, the spread of venom throughout human tissue has not yet been modeled. The goal of this study is to examine the contributions of relevant modes of mass transport on the spread of venom in human skeletal muscle tissue. In this study, computational models that mimic the localized propagation of venom were developed using parameter values for diffusivity, injection pressure, and injection volume determined from available research papers, empirical formulas, and clinical case studies. COMSOL Multiphysics 4.3b software was used to simulate the dissemination of venom from a fang into human flesh. A simplified 2D axisymmetric geometry was used initially to model the human tissue punctured by a single snake fang. This model allows us to examine the diffusion of BAP1 metalloprotease in human tissue. The results were compared to data from in vivo snake bite case studies and a study of the diffusion of similarly sized non-toxic protein. It was determined that diffusion alone could not be responsible for the expected extent of venom spread. Therefore, additional modes of mass transport, such as convection and Darcy’s flow, were evaluated and integrated in a 3D model of a human leg. Darcy flow at the point of injection simulated the effect of the injection pressure pushing venom out of the fang into the tissue. The model results were compared to findings in a series of studies on venom mechanics and metering in rattlesnakes and were found to be consistent. The convection of venom away from the injection site due to circulation of blood and interstitial fluid in the leg was modeled as a source term. Sensitivity analyses were performed in order to study how sensitive the solutions are to these input parameters. These models enable researchers to gain insight into how the different modes of mass transport influence the progression of edema. Knowing this can allow researchers to develop more effective treatment methods and antidotes for snakebites. Researchers can also modify these input parameters in order to model venom transport for different species of snakes, allowing them to tailor treatment methods for a variety of snakes.