Dynamic modeling of uteroplacental blood flow in IUGR indicates vortices and elevated pressure in the intervillous space – a pilot study

Abstract

Ischemic placental disease is a concept that links intrauterine growth retardation (IUGR) and preeclampsia (PE) back to insufficient remodeling of uterine spiral arteries. The rheological consequences of insufficient remodeling of uterine spiral arteries were hypothesized to mediate the considerably later manifestation of obstetric disease. However, the micro-rheology in the intervillous space (IVS) cannot be examined clinically and rheological animal models of the human IVS do not exist. Thus, an in silico approach was implemented to provide in vivo inaccessible data. The morphology of a spiral artery and the inflow region of the IVS were three-dimensionally reconstructed to provide a morphological stage for the simulations. Advanced high-end supercomputing resources were used to provide blood flow simulations at high spatial resolution. Our simulations revealed turbulent blood flow (high-velocity jets and vortices) combined with elevated blood pressure in the IVS and increased wall shear stress at the villous surface in conjunction with insufficient spiral artery remodeling only. Post-hoc histological analysis of uterine veins showed evidence of increased trophoblast shedding in an IUGR placenta. Our data support that rheological alteration in the IVS is a relevant mechanism linking ischemic placental disease to altered structural integrity and function of the placenta.

Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure

“…The model could be applied to compare normal and altered pregnancies, which may have different transfer efficiencies related both to changes in morphological structures and flow patterns. For example, in preeclampsia or intra uterine growth restriction (IUGR) the pressure in the intervillous space was estimated to be 5 to 10fold higher [13,18], and diabetic placentas display distinct differences in structure [25,26].…”

“…Recent advances in imaging technology have allowed 3D image based models to be developed. For example, maternal flow has been modelled to study the shear stress exerted by the maternal blood on the villous surface [12,13]. However, these studies did not include solute transport.…”

Maternal Hematological Parameters and Placental and Umbilical Cord Histopathology in Intrauterine Growth Restriction

“…The five cases did not coincide with notch in uterine arteries. With a mathematical model, it has been demonstrated that the vessel wall shear stress and blood velocity jets are bigger in uterine arteries in IUGR and also vortices occur more often in the intervillous space [28]. This condition of increased turbulence with increased platelet count promotes the formation of microthrombus that explains the intervillous deposition of fibrin and increased placental weight related to birth weight in IUGR pregnancies.…”

Go with the Flow—Trophoblasts in Flow Culture

“…Increased wall shear stress is suggested to act at the villous surface in the inflow regions of the intervillous space, where high wall shear stress could damage the villous trophoblast or at least affect its cellular turnover. This disturbance may be reflected in enhanced trophoblast shedding and elevated levels of free fetal DNA in the maternal circulation [ 32 ]. Paradoxically, increasing shear stress has been suggested to have a protective effect against induced apoptotic death in trophoblast cell lines [ 18 ].…”