Computational modelling of what matters for uterine vascular network function

Abstract

During pregnancy, maternal uterine vasculature adapts to supply the developing fetus with sufficient oxygen and nutrients for growth. In pregnancy conditions such as FGR and preeclampsia, the system is unable to make the necessary changes, leading to adverse health conditions for both the mother and the growing baby. During pregnancy, the vessels outwardly remodel reducing system resistance (along with an increase in maternal cardiac output), allowing for increased flow and the vascular reactivity behaviour of uterine vessels adapts. Detecting these vascular changes is difficult using Doppler ultrasound, with waveforms being a clinical indicator of downstream resistance. Additionally, animal models such as rats can inform the understanding of human physiology. Computational modelling was implemented in this study to link anatomical observations to physiological function. Firstly, static models spanning the first half of pregnancy were improved with novel anatomical data for vessel geometries and plug characteristics. The transformation of the uterine vasculature is dependent on placentation because placental trophoblast cells invade the spiral arteries (feed blood to the placenta) initially forming plugs to flow and transforming these vessels into funnels. The degradation of trophoblast plugs was considered with the inclusion of flow descriptions through clear channels with porous surrounds. A sensitivity analysis quantified the impact of individual parameters on the overall network function. The channels as modelled here supports that they are the dominant pathway for flow and the porous surrounds act as bottlenecks. Plugs reduce shear conditions in the upstream radial and arcuate arteries, while the uterine artery only depend on vessel lumen. Secondly, models of vascular reactivity (passive, active and shear responses) derived for rat radial arteries were parameterised for human vessels and incorporated into network models of uterine circulation at the radial artery levels (identified as key modulators of flow). Pregnancy adapts radial vessels to tolerate a higher flow rate before constricting, which is important for maintaining blood flow through to the placenta. In the network models, the passive response follows the trend of increasing vessel diameter with increasing pressure. When the active response is added, the myogenic response adds a constriction response, dampening the passive increase in diameter.