No abstract

Preeclampsia–eclampsia syndrome is a leading cause of maternal mortality. The precise etiology of preeclampsia is still not well‐defined and different forms exist, including early and late forms or preeclampsia, which may arise via distinctly different mechanisms. Low‐dose aspirin administered at the end of the first trimester in women identified as high risk has been shown to reduce the incidence of early, but not late, preeclampsia; however, current risk factors show only fair predictive capability. There is a pressing need to develop accurate descriptions for the different forms of preeclampsia. This paper presents 1D fluid, solid, growth, and remodeling models for pregnancies complicated with early and late forms of preeclampsia. Simulations affirm a broad set of literature results that early forms of preeclampsia are characterized by elevated uterine artery pulsatility index (UA‐PI) and total peripheral resistance (TPR) and lower cardiac output (CO), with modestly increased mean arterial blood pressure (MAP) in the first half of pregnancy, with elevation of TPR and MAP beginning at 20 weeks. Conversely, late forms of preeclampsia are characterized by only slightly elevated UA‐PI and normal pre‐term TPR, and slightly elevated MAP and CO throughout pregnancy, with increased TPR and MAP beginning after 34 weeks. Results suggest that preexisting arterial stiffness may be elevated in women that develop both early forms and late forms of preeclampsia; however, data that verify these results are lacking in the literature. Pulse wave velocity increases in early‐ and late‐preeclampsia, coincident with increases in blood pressure; however, these increases are mainly due to the strain‐stiffening response of larger arteries, rather than arterial remodeling‐derived changes in material properties. These simulations affirm that early forms of preeclampsia may be associated with abnormal placentation, whereas late forms may be more closely associated with preexisting maternal cardiovascular factors; simulations also highlight several critical gaps in available data.

Background: Lymphedema is a condition in which the two primary functions of the lymphatic system, immunity and lymph transport, are compromised. Computational models of lymphatic function to characterize lymph transport have proved useful in quantifying changes in lymph transport in health and disease; however, much is unknown regarding the regulation of contractions throughout a lymphatic network. The purpose of this paper is to study the role of pacemaking cells and contractile wave propagation on lymph transport using a 1-D mathematical model. Method: A 1D fluid-solid modeling framework with constitutive relationships were employed to characterize the interaction between the contracting vessel wall and the lymph flow during contractions. The time-space distribution of contraction waves along the length of a three-lymphangion chain, was determined by prescribing the location of pacemaking cells and parameters that govern the contractile wave propagation, with the total contractile response at each location determined as the summation of the local electrical signals. Results: Spatiotemporal changes in radius and lymphangion ejection fraction from our illustrative simulations mimic well values reported in isolated lymphatics from the wild-type (WT) and Smmhc-CreERT2;Cx45fx/fx knock-out (KO) reported in the literature. The flow rate is 5.43 and 2.45 μL⁄hr in the WT and the KO (average) models, respectively. The average and the peak WSS in the WT model are 0.08 and 4 dyn⁄(cm^2 ) and -0.03 and 0.87 dyn⁄(cm^2 ) in the KO (average) models, respectively. Conclusions: The factors that govern the timing of lymphatic contractions remain largely unknown; but these factors likely play a central role in health and disease. This modeling framework captures well lymphatic contractile wave propagations and how it relates to lymph transport and may motivate novel assays and experimental endpoints to evaluate subtle changes in lymphatic pumping function in the development and progression of lymphedema.