A 1D model characterizing the role of spatiotemporal contraction distributions on lymph transport.

Lymphedema is a condition in which lymph transport is compromised. The factors that govern the timing of lymphatic contractions are largely unknown; however, these factors likely play a central role in lymphatic health. Computational models have proven useful in quantifying changes in lymph transport; nevertheless, there is still much unknown regarding the regulation of contractions. The purpose of this paper is to utilize computational modeling to examine the role of pacemaking activity in lymph transport. A 1D fluid-solid modeling framework was utilized to describe the interaction between the contracting vessel and the lymph flow. The distribution of contractions along a three-lymphangion chain in time and space was determined by specifying the pacemaking sites and parameters obtained from experimentation. The model effectively replicates the contractility patterns in experiments. Quantitatively, the flow rates were measured at 5.44 and 2.29 [Formula: see text], and the EF values were 78% and less than 33% in the WT and KO models, respectively, which are consistent with the literature. Applying pacemaking parameters in this modeling framework effectively captures lymphatic contractile wave propagations and their relation to lymph transport. It can serve as a motivation for conducting novel studies to evaluate lymphatic pumping function during the development of lymphedema.

A mathematical model of vascular and hemodynamics changes in early and late forms of preeclampsia.

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.

A mathematical model of maternal vascular growth and remodeling and changes in maternal hemodynamics in uncomplicated pregnancy.

The maternal vasculature undergoes tremendous growth and remodeling (G&R) that enables a > 15-fold increase in blood flow through the uterine vasculature from conception to term. Hemodynamic metrics (e.g., uterine artery pulsatility index, UA-PI) are useful for the prognosis of pregnancy complications; however, improved characterization of the maternal hemodynamics is necessary to improve prognosis. The goal of this paper is to develop a mathematical framework to characterize maternal vascular G&R and hemodynamics in uncomplicated human pregnancies. A validated 1D model of the human vascular tree from the literature was adapted and inlet blood flow waveforms at the ascending aorta at 4 week increments from 0 to 40 weeks of gestation were prescribed. Peripheral resistances of each terminal vessel were adjusted to achieve target flow rates and mean arterial pressure at each gestational age. Vessel growth was governed by wall shear stress (and axial lengthening in uterine vessels), and changes in vessel distensibility were related to vessel growth. Uterine artery velocity waveforms generated from this model closely resembled ultrasound results from the literature. The literature UA-PI values changed significantly across gestation, increasing in the first month of gestation, then dramatically decreasing from 4 to 20 weeks. Our results captured well the time-course of vessel geometry, material properties, and UA-PI. This 1D fluid-G&R model captured the salient hemodynamic features across a broad range of clinical reports and across gestation for uncomplicated human pregnancy. While results capture available data well, this study highlights significant gaps in available data required to better understand vascular remodeling in pregnancy.