Computer models to study uterine activation at labour

Abstract

Improving our understanding of the initiation of labour is a major aim of modern obstetric research, in order to better diagnose and treat pregnant women in which the process occurs abnormally. In particular, increased knowledge will help us identify the mechanisms responsible for preterm labour, the single biggest cause of neonatal morbidity and mortality. Attempts to improve our understanding of the initiation of labour have been restricted by the inaccessibility of gestational tissues to study during pregnancy and at labour, and by the lack of fully informative animal models. However, computer modelling provides an exciting new approach to overcome these restrictions and offers new insights into uterine activation during term and preterm labour. Such models could be used to test hypotheses about drugs to treat or prevent preterm labour. With further development, an effective computer model could be used by healthcare practitioners to develop personalized medicine for patients on a pregnancy-by-pregnancy basis. Very promising work is already underway to build computer models of the physiology of uterine activation and contraction. These models aim to predict changes and patterns in uterine electrical excitation during term labour. There have been far fewer attempts to build computer models of the molecular pathways driving uterine activation and there is certainly scope for further work in this area. The integration of computer models of the physiological and molecular mechanisms that initiate labour will be particularly useful.

Propagation of electrical activity in uterine muscle during pregnancy: a review

“…Moreover, mechanical phenomena such as changes in uterine wall thickness during contractions and respiration-induced uterine wall movements can affect the interpretation of the uterine electrical activity recorded on the abdomen and should therefore be taken into account (de Lau et al 2013b. Finally, mathematical modelling of uterine electrical activity, especially when approached on a multi-scale point of view and empirically validated, can significantly contribute to increase knowledge on the link between non-invasive measurements, the underlying physiology and the onset of labour and to ensure reliable measurement by dedicated artefact modelling and removal (Rihana et al 2009, Aslanidi et al 2011, Laforet et al 2011, Sharp et al 2013.…”

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

“…However, to fully evaluate the actions of any tocolytic compounds, we need to also consider their effects at the tissue and organ levels. Currently there is no validated computational organ model for the uterus that would serve well this purpose although it is recognized by many that efforts toward this are required (Aslanidi et al, 2011a ; Sharp et al, 2013 ). We are under no illusion that there is a need for much more “wet” experimentation—particularly in USMCs—to furnish computational model improvement, and to test with increasing rigor and clarity, important hypotheses of relevance to tocolysis.…”

“…The uterus is also an electrically excitable tissue whose contractile function is determined by episodic spontaneous APs and calcium fluxes. Although our comprehension of the electrophysiological basis of uterine AP formation lags behind that of cardiac muscle, there is an increasing awareness that computational approaches, such as those which have been applied so extensively to cardiac muscle, may foster advances in this matter (Taggart et al, 2007 ; Aslanidi et al, 2011a ; Tong et al, 2011 ; Sharp et al, 2013 ). For example, we have developed a biophysically-detailed uterine smooth muscle cell (USMC) model validated against experimental data and it can describe many different uterine AP forms and the corresponding intracellular calcium changes (Tong et al, 2011 ).…”

Mathematical modeling of the female reproductive system: from oocyte to delivery

“…Understanding the electrophysiology of the uterus lags behind studies in other organs, such as the heart, and the contractile activity of the uterus is considered to be more complex than that of the heart . It is clear then that a multiscale and multigroup effort is required to build a picture of uterine electrophysiology that is able to closely represent the in vivo situation and to predict emergent function responsible for normal and abnormal labor . The most complete multiscale model to date includes a model of myocyte (cell‐level) electrical activity, coupled to a meso‐scale model of uterine muscle fibers to allow for different electrical conductivity along and across a fiber, and at the largest scale a simplified four compartment geometrical representation of the abdominal cavity, myometrium, amniotic fluid and fetus, through which an electromagnetic field is defined by Maxwell's equations .…”