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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 using the same seed values as in figure 4, and midrange parameter values.The periods between contractions varies only slightly. B, C, and D. Regional activities immediately prior to the 4th, 5th, and 6th contractions, respectively. Each of the three contractions has a different apparent pacemaker (arrow).
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pcbi-1003850-g005: A. Simulation using the same seed values as in figure 4, and midrange parameter values.The periods between contractions varies only slightly. B, C, and D. Regional activities immediately prior to the 4th, 5th, and 6th contractions, respectively. Each of the three contractions has a different apparent pacemaker (arrow).

Mentions: Next we demonstrate that it is possible for the simulation to generate contractions that are initiated by multiple pacemakers. In this run, the rows and columns are set to reflect 25 regions (rows = columns = 5) and the random number seeds for anatomy sensitivity and action potential thresholds are set to 1474 and 2500, respectively. Regular contractions are seen with only slight variations of the interval between contractions (Fig. 5A. The color animation of the regional activities reveals that the first region to demonstrate significant activity that continues through a global contraction is not always the same (Fig. 5 B, C, D).


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 using the same seed values as in figure 4, and midrange parameter values.The periods between contractions varies only slightly. B, C, and D. Regional activities immediately prior to the 4th, 5th, and 6th contractions, respectively. Each of the three contractions has a different apparent pacemaker (arrow).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003850-g005: A. Simulation using the same seed values as in figure 4, and midrange parameter values.The periods between contractions varies only slightly. B, C, and D. Regional activities immediately prior to the 4th, 5th, and 6th contractions, respectively. Each of the three contractions has a different apparent pacemaker (arrow).
Mentions: Next we demonstrate that it is possible for the simulation to generate contractions that are initiated by multiple pacemakers. In this run, the rows and columns are set to reflect 25 regions (rows = columns = 5) and the random number seeds for anatomy sensitivity and action potential thresholds are set to 1474 and 2500, respectively. Regular contractions are seen with only slight variations of the interval between contractions (Fig. 5A. The color animation of the regional activities reveals that the first region to demonstrate significant activity that continues through a global contraction is not always the same (Fig. 5 B, C, D).

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