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

ABSTRACT: 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.

SUBMITTER: Young RC

PROVIDER: S-EPMC4199482 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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

Young Roger C RC Barendse Peter P

PLoS computational biology 20141016 10

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, ...[more]

PMID: 25330227

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Project description:BackgroundMost labor-related problems can be attributed to the uterine myometrium muscle, as this irritable tissue must suppress its irritability potential during pregnancy. Unfortunately, fewer studies have investigated the causes of this lack of suppression in preterm labor.MethodsWe conducted a scoping narrative review using three online databases (PubMed, Scopus, and Science Direct).ResultsThe review focused on ion channel functions in the myometrium, including sodium channels [Na K-ATPase, Na-activated K channels (Slo2), voltage-gated (SCN) Na+, Na+ leaky channels, nonselective (NALCN) channels], potassium channels [KATP (Kir6) channels, voltage-dependent K channels (Kv4, Kv7, and Kv11), twin-pore domain K channels (TASK, TREK), inward rectifier Kir7.1, Ca2+-activated K+ channels with large (KCNMA1, Slo1), small (KCNN1-3), intermediate (KCNN4) conductance], and calcium channels [L-Type and T-type Ca2+ channels, calcium-activated chloride channels (CaCC)], as well as hyperpolarization-activated cation channels. These channels' functions are associated with hormonal effects such as oxytocin, estrogen/progesterone, and local prostaglandins.ConclusionElectromechanical/hormonal activity and environmental autocrine factors can serve as the primary practical basis for premature uterine contractions in term/preterm labor. Our findings highlight the significance of.1.the amplitude rate of hyperpolarization and the frequency of contractions,2.changes in the estrogen/progesterone ratio,3.Prostaglandins E/F involvement in initiating potential spikes and the increase of intracytoplasmic Ca2+.This narrative study highlights the range of hyperpolarization and the frequency of myometrium contractions as crucial factors. The synchronized complex progress of estrogen to progesterone ratio and prostaglandins plays a significant role in initiating potential spikes and increasing intracytoplasmic Ca2+, which further influences the contraction process during labor. Insights into myometrium physiology gained from this study may pave the way for much-needed new treatments to reduce problems associated with normal and preterm labor.

Dataset Information

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

Publications

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

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