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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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A. Simulation results using the default values.See Table 2 for complete set of input values. B. The action potential multiplier was changed to 2 from 3, simulating nifedipine exposure (all other input values remained the same as in A). C. The action potential multiplier was reduced further to 1.5, simulating increasing the nifedipine concentration.
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pcbi-1003850-g003: A. Simulation results using the default values.See Table 2 for complete set of input values. B. The action potential multiplier was changed to 2 from 3, simulating nifedipine exposure (all other input values remained the same as in A). C. The action potential multiplier was reduced further to 1.5, simulating increasing the nifedipine concentration.

Mentions: Here we describe the behavior of the simulation for specific input values (Table 2). In figure 3A the default values, 1.S1000:1.8/1/0.3; S2000:4/0.6/0.4, reveal a pressure profile suggestive of patterns commonly seen using pressure catheters on women in labor. Contractions are regular, although show some variability of the period between contractions. Peak heights vary slightly. Each contraction arises spontaneously. Pressure rises slowly at first, then accelerates. There is a pseudo-plateau, then a pseudo-symmetrical falling phase. Of note, the refractory time is set at 20 iterations, yet the number of steps between some contractions is ∼40.


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

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

A. Simulation results using the default values.See Table 2 for complete set of input values. B. The action potential multiplier was changed to 2 from 3, simulating nifedipine exposure (all other input values remained the same as in A). C. The action potential multiplier was reduced further to 1.5, simulating increasing the nifedipine concentration.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003850-g003: A. Simulation results using the default values.See Table 2 for complete set of input values. B. The action potential multiplier was changed to 2 from 3, simulating nifedipine exposure (all other input values remained the same as in A). C. The action potential multiplier was reduced further to 1.5, simulating increasing the nifedipine concentration.
Mentions: Here we describe the behavior of the simulation for specific input values (Table 2). In figure 3A the default values, 1.S1000:1.8/1/0.3; S2000:4/0.6/0.4, reveal a pressure profile suggestive of patterns commonly seen using pressure catheters on women in labor. Contractions are regular, although show some variability of the period between contractions. Peak heights vary slightly. Each contraction arises spontaneously. Pressure rises slowly at first, then accelerates. There is a pseudo-plateau, then a pseudo-symmetrical falling phase. Of note, the refractory time is set at 20 iterations, yet the number of steps between some contractions is ∼40.

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