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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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Two tissues linked end-to-end in isometric contractility experiment.A. Simulation where both tissues express repetitive contractions, but the tissues are contracting out-of-phase. B. Out-of-phase contractions experimentally recorded from two rat myometrial tissue strips demonstrating alternating contraction pattern corresponding to A (from ref. 16). “L” is the bioelectrical activity of the left tissue strip; “R” is the bioelectrical activity of the right tissue strip. C. Simulation after increasing the starting pressure, but keeping all other input values the same as in A, reveals in-phase contractions. D. Returning the starting pressure to the value in A, but decreasing the refractory duration also couples the tissue into an in-phase pattern.
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pcbi-1003850-g007: Two tissues linked end-to-end in isometric contractility experiment.A. Simulation where both tissues express repetitive contractions, but the tissues are contracting out-of-phase. B. Out-of-phase contractions experimentally recorded from two rat myometrial tissue strips demonstrating alternating contraction pattern corresponding to A (from ref. 16). “L” is the bioelectrical activity of the left tissue strip; “R” is the bioelectrical activity of the right tissue strip. C. Simulation after increasing the starting pressure, but keeping all other input values the same as in A, reveals in-phase contractions. D. Returning the starting pressure to the value in A, but decreasing the refractory duration also couples the tissue into an in-phase pattern.

Mentions: When rows = 1, columns = 2 there are two regions, which simulates two mechanically linked tissue strips (Fig. 7[16]. The anatomy seed and Weibull parameters are set to reflect both tissues with similar anatomy sensitivity values near 1 (0.986 and 0.989, respectively). The left and right tissues have action potential thresholds of 0.428 and 0.670, respectively, and the minimum pressure is set to fall between these values (0.5). In Fig. 7A the tissues appear to oscillate out of phase. The activity animation reveals that with these settings, the two regions are not ever highly active simultaneously (not shown) – first the “left” tissue becomes active, and then the “right”. This pattern correlates well with experimental observations (Fig. 7B) [16]. However, when the simulation is run with the starting pressure increased to 1 (Fig. 7C), the regions oscillate at the same time and the expressed pressure is large. It is also possible to coordinate the contractions by reducing the refractory duration to 10 (Fig. 7D, the starting pressure was returned to 0.5).


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

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

Two tissues linked end-to-end in isometric contractility experiment.A. Simulation where both tissues express repetitive contractions, but the tissues are contracting out-of-phase. B. Out-of-phase contractions experimentally recorded from two rat myometrial tissue strips demonstrating alternating contraction pattern corresponding to A (from ref. 16). “L” is the bioelectrical activity of the left tissue strip; “R” is the bioelectrical activity of the right tissue strip. C. Simulation after increasing the starting pressure, but keeping all other input values the same as in A, reveals in-phase contractions. D. Returning the starting pressure to the value in A, but decreasing the refractory duration also couples the tissue into an in-phase pattern.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003850-g007: Two tissues linked end-to-end in isometric contractility experiment.A. Simulation where both tissues express repetitive contractions, but the tissues are contracting out-of-phase. B. Out-of-phase contractions experimentally recorded from two rat myometrial tissue strips demonstrating alternating contraction pattern corresponding to A (from ref. 16). “L” is the bioelectrical activity of the left tissue strip; “R” is the bioelectrical activity of the right tissue strip. C. Simulation after increasing the starting pressure, but keeping all other input values the same as in A, reveals in-phase contractions. D. Returning the starting pressure to the value in A, but decreasing the refractory duration also couples the tissue into an in-phase pattern.
Mentions: When rows = 1, columns = 2 there are two regions, which simulates two mechanically linked tissue strips (Fig. 7[16]. The anatomy seed and Weibull parameters are set to reflect both tissues with similar anatomy sensitivity values near 1 (0.986 and 0.989, respectively). The left and right tissues have action potential thresholds of 0.428 and 0.670, respectively, and the minimum pressure is set to fall between these values (0.5). In Fig. 7A the tissues appear to oscillate out of phase. The activity animation reveals that with these settings, the two regions are not ever highly active simultaneously (not shown) – first the “left” tissue becomes active, and then the “right”. This pattern correlates well with experimental observations (Fig. 7B) [16]. However, when the simulation is run with the starting pressure increased to 1 (Fig. 7C), the regions oscillate at the same time and the expressed pressure is large. It is also possible to coordinate the contractions by reducing the refractory duration to 10 (Fig. 7D, the starting pressure was returned to 0.5).

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