Linking myometrial physiology to intrauterine pressure; how tissue-level contractions create uterine contractions of labor.

The mechanisms used to coordinate uterine contractions are not known. We develop a new model based on the proposal that there is a maximum distance to which action potentials can propagate in the uterine wall. This establishes "regions", where one action potential burst can rapidly recruit all the tissue. Regions are recruited into an organ-level contraction via a stretch-initiated contraction mechanism (myometrial myogenic response). Each uterine contraction begins with a regional contraction, which slightly increases intrauterine pressure. Higher pressure raises tension throughout the uterine wall, which initiates contractions of more regions and further increases pressure. The positive feedback synchronizes regional contractions into an organ-level contraction. Cellular automaton (CA) simulations are performed with Mathematica. Each "cell" is a region that is assigned an action potential threshold. An anatomy sensitivity factor converts intrauterine pressure to regional tension through the Law of Laplace. A regional contraction occurs when regional tension exceeds regional threshold. Other input variables are: starting and minimum pressure, burst and refractory period durations, enhanced contractile activity during an electrical burst, and reduced activity during the refractory period. Complex patterns of pressure development are seen that mimic the contraction patterns observed in laboring women. Emergent behavior is observed, including global synchronization, multiple pace making regions, and system memory of prior conditions. The complex effects of nifedipine and oxytocin exposure are simulated. The force produced can vary as a nonlinear function of the number of regions. The simulation directly links tissue-level physiology to human labor. The concept of a uterine pacemaker is re-evaluated because pace making activity may occur well before expression of a contraction. We propose a new classification system for biological CAs that parallels the 4-class system of Wolfram. However, instead of classifying the rules, biological CAs should classify the set of input values for the rules that describe the relevant biology.