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

Young RC, Barendse P - PLoS Comput. Biol. (2014)

Bottom Line: 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.The complex effects of nifedipine and oxytocin exposure are simulated.However, instead of classifying the rules, biological CAs should classify the set of input values for the rules that describe the relevant biology.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.

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.

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Flowchart of cellular automaton simulation.
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pcbi-1003850-g001: Flowchart of cellular automaton simulation.

Mentions: For human labor, the contractile state of the uterus and the intrauterine pressure are of primary concern. Since the intrauterine pressure is shared by all regions of the uterine wall regardless of relative location, we weight the nearest neighbors no more or less than the other regions. The CA rules approach to simulation is computationally efficient but, more importantly, emphasizes the physiological properties of the tissues that make up the organ. With this in mind, we define three specific rules (see flowchart figure 1): 1) Intrauterine pressure at each time step is calculated as a function of the regional contractile activities. 2) At the next time step, the intrauterine pressure sets the passive tension on each region according to the Law of Laplace. 3) Within regions, electrical activity creates contractile activity (defined as the tension of a contraction). The tension on each region will initiate and maintain an action potential burst if it exceeds a defined threshold (action potential threshold). By definition, if any part of a region experiences an action potential, the action potential travels throughout the entire region, but no farther, and the region contracts as a unit. When a region is experiencing an action potential burst, the contractile activity is calculated by multiplying the passive tension by the action potential multiplier (a factor >1). Each region can remain electrically active no more than a defined number of time steps (burst duration). If a region has been electrically active for the maximum allowable number of time steps, it enters a refractory period. When a region is in the refractory period, the tension is decreased by multiplying the passive tension by a factor <1 (refractory multiplier). The refractory period lasts a defined number of time steps (refractory duration – not shown in figure 1), then the region reverts back to expressing the passive tension.


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

Young RC, Barendse P - PLoS Comput. Biol. (2014)

Flowchart of cellular automaton simulation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199482&req=5

pcbi-1003850-g001: Flowchart of cellular automaton simulation.
Mentions: For human labor, the contractile state of the uterus and the intrauterine pressure are of primary concern. Since the intrauterine pressure is shared by all regions of the uterine wall regardless of relative location, we weight the nearest neighbors no more or less than the other regions. The CA rules approach to simulation is computationally efficient but, more importantly, emphasizes the physiological properties of the tissues that make up the organ. With this in mind, we define three specific rules (see flowchart figure 1): 1) Intrauterine pressure at each time step is calculated as a function of the regional contractile activities. 2) At the next time step, the intrauterine pressure sets the passive tension on each region according to the Law of Laplace. 3) Within regions, electrical activity creates contractile activity (defined as the tension of a contraction). The tension on each region will initiate and maintain an action potential burst if it exceeds a defined threshold (action potential threshold). By definition, if any part of a region experiences an action potential, the action potential travels throughout the entire region, but no farther, and the region contracts as a unit. When a region is experiencing an action potential burst, the contractile activity is calculated by multiplying the passive tension by the action potential multiplier (a factor >1). Each region can remain electrically active no more than a defined number of time steps (burst duration). If a region has been electrically active for the maximum allowable number of time steps, it enters a refractory period. When a region is in the refractory period, the tension is decreased by multiplying the passive tension by a factor <1 (refractory multiplier). The refractory period lasts a defined number of time steps (refractory duration – not shown in figure 1), then the region reverts back to expressing the passive tension.

Bottom Line: 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.The complex effects of nifedipine and oxytocin exposure are simulated.However, instead of classifying the rules, biological CAs should classify the set of input values for the rules that describe the relevant biology.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.

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.

Show MeSH
Related in: MedlinePlus