ИСТИНА

1. Introduction Left ventricular assist devices (LVADs) provide a viable therapy for patients with end-stage heart failure. However, complications related to thrombosis reduce the effectiveness of using such devices. Device-generated pathological shear stress patterns are believed to cause thrombus formation due to platelet activation. Shear stress in general acts similar to platelets chemical agonists, i.e. platelet activation intensity depends on the magnitude and time of exposure to pathological shear stress [1]. The key mediator transmitting the effect of shear stress to intracellular platelet activation pathways is von Willebrand factor (VWF) [2]. The purpose of this study is to develop a mathematical model of shear-induced platelet activation in intensive blood flows. It takes into account effects of the shear stress and VWF molecule unwinding. 2. Materials and Methods The platelet activation model includes two groups of equations: equations of motion that govern the blood flow and a set of coupled convection-diffusion-reaction equations that determine transport and inter-conversion of chemical species. The kinetics of platelet transition to the activated state is assumed to be dependent on the concentration of resting platelets and unwinding of grafted on platelet surface VWF molecules with different degree of multimerization. Achievement of a certain critical value by the shear stress serves as a condition of transition of resting platelets to the activated state. The degree of the VWF unwinding is considered to depend on the shear stress in accordance with the work [3]. 3. Results The model was applied to investigation of platelet activation in test device FDA Blood Pump [4]. k-omega SST model was used to account for turbulence. The results of calculations showed that presence of significant turbulent stresses can provoke “volumetric” platelets activation when the activation zones are concentrated far from walls of device. 4. Discussion and Conclusions The model of shear-induced platelet activation providing the opportunity to analyze the influence of chemical and hemodynamic stimuli on thrombosis kinetics was described. The model can be used for evaluating the thrombogenicity of LVADs. 5. References 1. Kroll MH et al., Blood; 88(5):1525-41 (1996). 2. Springer TA, Blood; 124(9):1412-25 (2014). 3. Zlobina KE, Guria GT, Sci Rep; 6(30508): srep30508 (2016). 4. Malinauskas RA et al., ASAIO Journal; 63(2):150-160 (2017).